A questionnaire-based audit to assess overall experience and convenience among patients using vaginal progesterone tablets (Lutigest®) for luteal phase support during IVF treatment

PubMed Central

Heine, Polly; Sellar, Laura; Whitten, Sue; Bajaj, Priti

2017-01-01

Purpose The aim of this audit was to assess the overall experience and patient convenience of vaginal progesterone tablets (Lutigest®, marketed as Endometrin® in the USA) used for luteal phase support (LPS) during in vitro fertilization (IVF) treatment. Patients and methods This questionnaire-based audit included responses from 100 patients undergoing IVF treatment at six IVF clinics in the UK from September 2015 to November 2016. Fourteen days after starting progesterone supplementation for LPS during their IVF treatment, patients rated overall experience and perceived convenience of the prescribed progesterone by completing a questionnaire. Results Of the 100 patients included, 96 received vaginal progesterone tablets for LPS. Overall, 53.1% (51/96) indicated that the progesterone tablets were “very easy” to use; 42.7% (41/96) and 44.8% (43/96) found it “very convenient” or “neither convenient or inconvenient” to administer the tablet, respectively. Overall experience with using progesterone tablets was rated as “very comfortable” by 34.4% (33/96) and “neither comfortable or uncomfortable” by 56.3% (54/96) of patients. The applicator was used by 93.8% (90/96) of patients to administer the tablet, and 86.5% (83/96) indicated that the applicator was easy to clean for repeated use. A total of 33 patients had a previous IVF cycle during which they were prescribed vaginal progesterone pessaries for LPS. Compared with progesterone pessaries, the majority found treatment with progesterone tablets to be more comfortable (60.6%; 20/33) and more convenient (57.6%; 19/33) and indicated that the progesterone tablet was their preferred progesterone formulation for LPS (60.6%; 20/33). Conclusion These findings offer insights into real-world patient experiences with the progesterone vaginal tablet formulation. The results suggest overall patient convenience, ease, and comfort with using progesterone vaginal tablets for LPS. The majority of patients found

The prevalence of short cervix between 20 and 24 weeks of gestation and vaginal progesterone for prolonging of gestation.

PubMed

Maerdan, Malipati; Shi, Chunyan; Zhang, Xiaoxiao; Fan, Lixin

2017-07-01

The objective of this study is to understand the prevalence of short cervical length between 20 and 24 weeks gestation in China and to evaluate the efficacy of micronized progesterone for prolonging gestation in nulliparous patients with a short cervix. From May 2010 to May 2015, a total of 25 328 asymptomatic women with singleton pregnancies at Peking University First Hospital had their cervical length routinely measured between 20 and 24 weeks of gestation. A cervical length of 25 mm or less was defined as a shortened cervical length. The therapies prescribed include vaginal micronized progesterone capsules (200 mg each night) or bed rest from 20 to 34 weeks of gestation. The primary outcome was spontaneous delivery before 33 weeks. (1) One hundred fourteen women had a cervical length of ≤25 mm (0.45%). (2) Twenty-nine of which with previous spontaneous preterm delivery or late pregnancy loss had cervical cerclage, the remaining 85 women by the use of vaginal progesterone or simply resting activity restriction to prevent preterm birth. (3) In 85 nulliparous women treated by progesterone or bed rest, progesterone use in cervical length between 10 and 20 mm was associated with a statistically significant reduction in the incidence of preterm birth at <33 weeks of gestation (9.5% versus 45.5%, p = 0.02) compared with bed rest. There were no significant differences in cervical length between 20 and 25 mm in their rates of spontaneous preterm delivery at <33 (5.3% versus 3.2%, p = 0.72), <37 (33.3% versus 54.5%, p = 0.25), or <35 weeks (14.3% versus 45.5, p = 0.06) of gestation between vaginal progesterone and bed rest. The rate of short cervical length was less than expected. Vaginal progesterone is efficacious for the prolonging of gestation in women with a cervical length of 10-20 mm in the mid-trimester for a singleton gestation and nulliparous women. For a cervical length of 20-25 mm in the mid trimester, vaginal progesterone

Growth of Normal Mouse Vaginal Epithelial Cells in and on Collagen Gels

NASA Astrophysics Data System (ADS)

Iguchi, Taisen; Uchima, Francis-Dean A.; Ostrander, Patricia L.; Bern, Howard A.

1983-06-01

Sustained growth in primary culture of vaginal epithelial cells from ovariectomized adult BALB/cCrg1 mice embedded within or seeded on collagen gel matrix was achieved in a serum-free medium composed of Ham's F-12 medium/Dulbecco's modified Eagle's medium, 1:1 (vol/vol), supplemented with insulin, bovine serum albumin fraction V, epidermal growth factor, cholera toxin, and transferrin. Three-dimensional growth of vaginal epithelial cells occurred inside the collagen gel matrix. Cell numbers increased 4- to 8-fold in collagen gel and about 4-fold on collagen gel after 9-10 days in culture. The effect of 17β -estradiol (0.00018-180 nM in gel or 0.018-180 nM on gel) and diethylstilbestrol (DES; 0.0186-186 nM in gel) on the growth of vaginal epithelial cells was examined. The addition of estrogen did not enhance the growth of vaginal epithelial cells during this time period either in the complete medium or in a suboptimal medium. Cultures on floating collagen gels in the serum-free medium are composed of 1-3 cell layers with superficial cornification. Estrogen does not appear to be a direct mitogen for vaginal epithelial cells, at least in this system.

78 FR 19271 - Draft Guidance for Industry on Bioequivalence Recommendations for Metronidazole Vaginal Gel...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-29

... Metronidazole Vaginal Gel; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The... entitled ``Bioequivalence Recommendations for Metronidazole Vaginal Gel.'' The guidance provides specific...) for metronidazole vaginal gel. DATES: Although you can comment on any guidance at any time (see 21 CFR...

Formulation development and evaluation of innovative two-polymer (SR-2P) bioadhesive vaginal gel.

PubMed

Podaralla, Satheesh; Alt, Carsten; Shankar, Gita N

2014-08-01

The main objective of this investigation was to study the feasibility of developing a vaginal bioadhesive microbicide using a SRI's proprietary two-polymer gel platform (SR-2P). Several formulations were prepared with different combinations of temperature-sensitive polymer (Pluronic® F-127) and mucoadhesive polymer (Noveon® AA-1), producing gels of different characteristics. Prototype polymeric gels were evaluated for pH, osmolality, buffering capacity, and viscosity under simulated vaginal semen dilutions, and bioadhesivity using ex vivo mini pig vaginal tissues and texture analyzer. The pH of the polymeric gel formulations ranged from 5.1 to 6.4; the osmolality varied from 13 to 173 mOsm. Absolute viscosity ranged from 513 to 3,780 cPs, and was significantly reduced (1.5- to 3-fold) upon incubation with simulated vaginal and semen fluid mixture. Among the tested gels (indicated in the middle row as a molar ratio of a mixture of Noveon vs. Pluronic), only SR-2P retained gel structure upon dilution with simulated fluids and mild simulated coital stress. The pH of the SR-2P gel was maintained at about 4.6 in simulated vaginal fluid and also showed high peak force of adhesion in mini pig vaginal tissue. Furthermore, SR-2P gel caused no or only minimal irritation in a mouse vaginal irritation model. The results of this preliminary study demonstrated the potential application of SR-2P gel as a vaginal microbicide vehicle for delivery of anti-HIV agents.

Pilot randomized trial for treatment of bacterial vaginosis using in situ forming metronidazole vaginal gel.

PubMed

Shaaban, Omar M; Fetih, Gihan N; Abdellah, Noura H; Ismail, Saeyd; Ibrahim, Maggie A; Ibrahim, El-sayed A

2011-07-01

To compare the efficacy of a novel vaginal delivery system for metronidazole (0.8% MTZ in situ gel) versus a conventional MTZ vaginal gel product in the treatment of bacterial vaginosis (BV). All consecutive patients who presented to a tertiary care hospital with symptoms suggestive of BV were approached to participate in the study. Forty-two eligible participants were randomly assigned to either MTZ in situ gel or a conventional vaginal gel product twice daily for 5 days. All participants were re-examined after one and 4 weeks of the beginning of treatment to ensure cure of infection and any side-effects. Demographic criteria of the participants were comparable in the two treatment groups. The cure rate after one week from the treatment was 85% in the in situ gel group and 71.4% in the conventional vaginal gel group (P = 0.294), while after 4 weeks, the cure rate showed significant difference in the in situ gel group as compared to the conventional vaginal gel group (16/20 [80%]) and (9/19 [47.4%]), respectively (P = 0.034). Pilot testing showed that in situ MTZ vaginal gel is more effective than the conventional vaginal gel for long-term cure of BV. These findings suggest a novel and efficient long-term treatment of BV. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials.

PubMed

Saccone, G; Khalifeh, A; Elimian, A; Bahrami, E; Chaman-Ara, K; Bahrami, M A; Berghella, V

2017-03-01

Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB. Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB < 34 weeks. Secondary outcomes were SPTB < 37 weeks, < 32 weeks, < 28 weeks and < 24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% CI. Risk of bias for each included study was assessed. Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily, one used 100 mg suppository daily and one used 200 mg suppository daily. All included RCTs used 250 mg intramuscular 17-OHPC weekly in the comparison group. Women who received vaginal progesterone had significantly lower rates of SPTB < 34 weeks (17.5% vs 25.0%; RR, 0.71 (95% CI, 0.53-0.95); low quality of evidence) and < 32 weeks (8.9% vs 14.5%; RR, 0.62 (95% CI, 0.40-0.94); low quality of evidence) compared with women who received 17-OHPC. There were no significant differences in the rates of SPTB < 37 weeks, < 28 weeks and < 24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal progesterone group compared with the 17-OHPC group (7.1% vs 13.2%; RR, 0

Population differences and the effect of vaginal progesterone on preterm birth in women with threatened preterm labor (.).

PubMed

Hermans, Frederik Jan Robin; Karolinski, Ariel; Othenin-Girard, Véronique; Bertolino, María Victoria; Schuit, Ewoud; Salgado, Pablo; Hösli, Irene; Irion, Olivier; Laterra, Cristina; Mol, Ben Willem J; Martinez de Tejada, Begoña

2016-10-01

Threatened preterm labor (tPTL) is a complication of pregnancy. Identification of women and clinical definition differs between countries. This study investigated differences in tPTL and effectiveness of vaginal progesterone to prevent preterm birth (PTB) between two countries. Secondary analysis of a randomized controlled trial (RCT) from Argentina and Switzerland comparing vaginal progesterone to placebo in women with tPTL (n = 379). Cox proportional hazards analysis was performed to compare placebo groups of both countries and to compare progesterone to placebo within each country. We adjusted for baseline differences. Iatrogenic onset of labor or pregnancy beyond gestational age of interest was censored. Swiss and Argentinian women were different on baseline. Risks for delivery <14 days and PTB < 34 and < 37 weeks were increased in Argentina compared to Switzerland, HR 3.3 (95% CI 0.62-18), 54 (95% CI 5.1-569) and 3.1 (95% CI 1.1-8.4). In Switzerland, progesterone increased the risk for delivery <14 days [HR 4.4 (95% CI 1.3-15.7)] and PTB <37 weeks [HR 2.5 (95% CI 1.4-4.8)], in Argentina there was no such effect. In women with tPTL, the effect of progesterone may vary due to population differences. Differences in populations should be considered in multicenter RCTs.

Vaginal progesterone to prevent preterm birth in pregnant women with a sonographic short cervix: clinical and public health implications.

PubMed

Conde-Agudelo, Agustin; Romero, Roberto

2016-02-01

Vaginal progesterone administration to women with a sonographic short cervix is an efficacious and safe intervention used to prevent preterm birth and neonatal morbidity and mortality. The clinical and public health implications of this approach in the United States have been critically appraised and compared to other therapeutic interventions in obstetrics. Vaginal progesterone administration to women with a transvaginal sonographic cervical length (CL) ≤25 mm before 25 weeks of gestation is associated with a significant and substantial reduction of the risk for preterm birth from <28 to <35 weeks of gestation, respiratory distress syndrome, composite neonatal morbidity and mortality, admission to the neonatal intensive care unit, and mechanical ventilation. These beneficial effects have been achieved in women with a singleton gestation, with or without a history of spontaneous preterm birth, and did not differ significantly as a function of CL (<10 mm, 10-20 mm, or 21-25 mm). The number of patients required for treatment to prevent 1 case of preterm birth or adverse neonatal outcomes ranges from 10-19 women. The number needed to screen for the prevention of 1 case of preterm birth before 34 weeks of gestation is 125 women, and 225 for the prevention of 1 case of major neonatal morbidity or neonatal mortality. Several cost-effectiveness and decision analyses have shown that the combination of universal transvaginal CL screening and vaginal progesterone administration to women with a short cervix is a cost-effective intervention that prevents preterm birth and associated perinatal morbidity and mortality. Universal assessment of CL and treatment with vaginal progesterone for singleton gestations in the United States would result in an annual reduction of approximately 30,000 preterm births before 34 weeks of gestation and of 17,500 cases of major neonatal morbidity or neonatal mortality. In summary, there is compelling evidence to recommend universal transvaginal

The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and clomiphene citrate/intra-uterine insemination cycles in unexplained infertility: A prospective randomised study.

PubMed

Karadag, Burak; Dilbaz, Berna; Karcaaltincaba, Deniz; Sahin, Elif Gulsah; Ercan, Fedi; Karasu, Yetkin; Tonyalı, Nazan Vanlı

2016-08-01

The purpose of this study is to analyse the effect of luteal-phase support on pregnancy rates in gonadotropin + intra-uterine insemination (Gn/IUI) and clomiphene citrate (CC) +IUI (CC/IUI) cycles in patients with unexplained infertility. Equal numbers of patients were recruited in two treatment arms (CC/IUI and Gn/IUI) (n = 100, n = 100, respectively). In each group, 50 patients received vaginal progesterone for 14 days (Crinone 8% vaginal gel, 90 mg per day) for luteal-phase support from the day after IUI and continued until menstruation or the 10th week of gestation if pregnant. There were 29 clinical pregnancies among 200 patients. Pregnancy rates were 12% in CC/IUI cycles, 10% in luteal-phase-supported CC/IUI cycles 16% in Gn/IUI cycles and 20% in luteal-phase-supported Gn/IUI cycles. Although pregnancy rates were higher in Gn/IUI cycles compared to CC/IUI cycles, luteal-phase support did not significantly affect the pregnancy rates in both groups. This study implies that luteal-phase support with progesterone has no pronounced beneficial effect on pregnancy rates in either CC/IUI or Gn/IUI cycles in patients with unexplained infertility.

Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation.

PubMed

Rençber, Seda; Karavana, Sinem Yaprak; Şenyiğit, Zeynep Ay; Eraç, Bayri; Limoncu, Mine Hoşgör; Baloğlu, Esra

2017-06-01

The purpose of this study was to develop a suitable mucoadhesive in situ gel formulation of clotrimazole (CLO) for the treatment of vaginal candidiasis. For this aim, the mixture of poloxamer (PLX) 407 and 188 were used to prepare in situ gels. Hydroxypropyl methylcellulose (HPMC) K100M or E50 was added to in situ gels in 0.5% ratio to improve the mucoadhesive and mechanical properties of formulations and to prolong the residence time in vaginal cavity. After the preparation of mucoadhesive in situ gels; gelation temperature/time, viscosity, mechanical, mucoadhesive, syringeability, spreadibility and rheological properties, in vitro release behavior, and anticandidal activities were determined. Moreover vaginal retention of mucoadhesive in situ gels was investigated with in vivo distribution studies in rats. Based on the obtained results, it was found that gels prepared with 20% PLX 407, 10% PLX 188 and 0.5% HPMC K100M/E50 might be suitable for vaginal administration of CLO. In addition, the results of in vivo distribution studies showed that gel formulations remained on the vaginal mucosa even 24 h after application. In conclusion, the mucoadhesive in situ gels of CLO would be alternative candidate for treatment of vaginal candidiasis since it has suitable gel properties with good vaginal retention.

Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial.

PubMed

Norman, Jane Elizabeth; Marlow, Neil; Messow, Claudia-Martina; Shennan, Andrew; Bennett, Phillip R; Thornton, Steven; Robson, Stephen C; McConnachie, Alex; Petrou, Stavros; Sebire, Neil J; Lavender, Tina; Whyte, Sonia; Norrie, John

2016-05-21

Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child. We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373. Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

PubMed

Palacio, M; Cobo, T; Antolín, E; Ramirez, M; Cabrera, F; Mozo de Rosales, F; Bartha, J L; Juan, M; Martí, A; Oros, D; Rodríguez, À; Scazzocchio, E; Olivares, J M; Varea, S; Ríos, J; Gratacós, E

2016-11-01

To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. Multicentre, randomised, double-blind, placebo-controlled trial. Twelve tertiary care centres in Spain. A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. Maintenance progesterone in 258 women after arrested PTL showed no benefit. © 2016 Royal College of Obstetricians and Gynaecologists.

Metronidazole with Lactacyd vaginal gel in bacterial vaginosis.

PubMed

Decena, Ditas Cristina D; Co, Jennifer T; Manalastas, Ricardo M; Palaypayon, Evelyn P; Padolina, Christia S; Sison, Judith M; Dancel, Louella A; Lelis, Marievi A

2006-04-01

To assess the efficacy and tolerability of lactic acid (Lactacyd vaginal gel; LVG) when given as an adjunct to metronidazole in the treatment of bacterial vaginosis (BV) among Filipino patients. A multicenter, open-labeled, controlled, randomized, three-arm comparative study on 90 women aged 18 years or over with clinically and microbiologically proven BV. The lactobacilli colony count significantly increased over time in all three arms. At day 14, growth of lactobacilli was significantly higher among patients in the lactic acid gel and combination treatment arms. Significant reduction of malodorous vaginal discharge (whiff test) and lowest recurrence of BV were noted in the metronidazole plus lactic acid gel arm. Regarding disappearance of signs of BV, there was significant decrease in the pH level and frequency of clue cell positive patients across time but was not significantly different across treatment groups. Only one patient (3%, 1/60) among those who received lactic acid gel complained of increased curd-like discharge. Six patients (10%, 6/60) who received metronidazole complained of epigastric pain/discomfort, dizziness and dyspnea. Lactic acid gel (LVG) is safe and as efficacious as metronidazole in the treatment of BV. There is evidence that LVG when combined with metronidazole is superior to metronidazole alone in promoting lactobacilli colonization. LVG as an adjunct to metronidazole, having the least number of recurrent BV, appears to result in better long-term treatment effect on bacterial vaginosis.

17-alpha-hydroxyprogesterone caproate versus vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix: A randomized controlled trial.

PubMed

Pirjani, Reihaneh; Heidari, Reza; Rahimi-Foroushani, Abbas; Bayesh, Seyedehsara; Esmailzadeh, Arezoo

2017-01-01

The aim of this study was to compare 17-alpha-hydroxyprogesterone caproate (17OHP-C) with vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix and to evaluate the changes of the cervical length (CL) over time. In this prospective randomized controlled trial, eligible patients were asymptomatic pregnant women with a sonographically short cervix. The participants in group 1 (n = 147) received vaginal progesterone suppositories at a dose of 400 mg daily and the women in group 2 (n = 150) received an i.m. dose of 250 mg 17OHP-C once a week. Transvaginal sonography was repeated every 3 weeks until 36 gestational weeks or the occurrence of preterm labor. A total of 304 singleton pregnant women between 16 and 24 gestational weeks with CL < 25 mm were enrolled in our study. The rates of preterm birth were 10.4% in the progesterone group and 14% in the 17OHP-C group: a difference that was not statistically significant (P = 0.416). Moreover, 264 participants underwent ultrasound examination five times and CL changes were studied for 15 weeks. The results showed that the CL changes over 15 weeks were statistically significant (P < 0.001), but the method of intervention (progesterone/17OHP-C) had no significant effect on CL change (P = 0.64). Our findings showed that vaginal progesterone and 17OHP-C had the same effect on the risk of preterm labor in asymptomatic women with a sonographically short cervix. We detected no significant difference between the effect of 17OHP-C and vaginal progesterone on CL changes over time. © 2016 Japan Society of Obstetrics and Gynecology.

VAGINAL PROGESTERONE VERSUS CERVICAL CERCLAGE FOR THE PREVENTION OF PRETERM BIRTH IN WOMEN WITH A SONOGRAPHIC SHORT CERVIX, SINGLETON GESTATION, AND PREVIOUS PRETERM BIRTH: A SYSTEMATIC REVIEW AND INDIRECT COMPARISON META-ANALYSIS

PubMed Central

CONDE-AGUDELO, Agustin; ROMERO, Roberto; NICOLAIDES, Kypros; CHAIWORAPONGSA, Tinnakorn; O'BRIEN, John M.; CETINGOZ, Elcin; DA FONSECA, Eduardo; CREASY, George; SOMA-PILLAY, Priya; FUSEY, Shalini; CAM, Cetin; ALFIREVIC, Zarko; HASSAN, Sonia S.

2012-01-01

OBJECTIVE No randomized controlled trial has directly compared vaginal progesterone and cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone versus cerclage, using placebo/no cerclage as the common comparator. STUDY DESIGN Adjusted indirect meta-analysis of randomized controlled trials. RESULTS Four studies evaluating vaginal progesterone versus placebo (158 patients) and five evaluating cerclage versus no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in reducing preterm birth or adverse perinatal outcomes. CONCLUSION Based on state-of-the-art methodology for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous preterm birth. The selection of the optimal treatment may depend upon adverse events, cost and patient/clinician preferences. PMID:23157855

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

PubMed

Martinez de Tejada, B; Karolinski, A; Ocampo, M C; Laterra, C; Hösli, I; Fernández, D; Surbek, D; Huespe, M; Drack, G; Bunader, A; Rouillier, S; López de Degani, G; Seidenstein, E; Prentl, E; Antón, J; Krähenmann, F; Nowacki, D; Poncelas, M; Nassif, J C; Papera, R; Tuma, C; Espoile, R; Tiberio, O; Breccia, G; Messina, A; Peker, B; Schinner, E; Mol, B W; Kanterewicz, L; Wainer, V; Boulvain, M; Othenin-Girard, V; Bertolino, M V; Irion, O

2015-01-01

To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour. © 2014 Royal College of Obstetricians and Gynaecologists.

Detection of estrus in dairy cows by electrical measurements of vaginal mucus and by milk progesterone.

PubMed

Gartland, P; Schiavo, J; Hall, C E; Foote, R H; Scott, N R

1976-05-01

Electrical resistance (ohms) of mucus were analyzed in 20 postpartum Holstein cows by use of a probe inserted into the anterior vagina every other day for 30 days. Composite milk samples were taken on the same day, and progesterone was determined by radioimmunoassay. Cows were observed twice daily for standing estrus and reproductive organs palpated weekly per rectum (rectal palpation). Fifteen cows which were cycling showed increasing progesterone 6 to 7 days after the onset of estrus with values of 8.1 to 10.0 ng progesterone/ml milk on days 10 to 17. Concentrations had declined rapidly 2 days before onset of the next estrus. Progesterone in milk was affected by cow and by day of the cycle. Electrical resistance followed a similar cyclical pattern, but variability was large and only cows differed. The correlation between milk progesterone and mucus resistance was .22. Progesterone concentrations for four cows with follicular cysts fluctuated randomly with a mean of 2.6 ng/ml. Mean resistance of vaginal mucus was 44 omega for both cycling and cystic cows, indicating that a single measurement of electrical resistance every 2nd day was unreliable in distinguishing physiological states. One cow had high progesterone in milk on days 19 to 25 and was diagnosed pregnant by rectal palpation 3 wk later. Cows were not seen in estrus 28% of the time when milk progesterone and rectal palpation indicated they were in the follicular phase of the estrous cycle and were cycling.

Induction of labor using prostaglandin vaginal gel: cost analysis comparing early amniotomy with repeat prostaglandin gel.

PubMed

Beckmann, Michael; Merollini, Katharina; Kumar, Sailesh; Flenady, Vicki

2016-04-01

In a randomized controlled trial of two policies for induction of labor (IOL) using Prostaglandin E2 (PGE2) vaginal gel, women who had an earlier amniotomy experienced a shorter IOL-to-birth time. To report the cost analysis of this trial and determine if there are differences in healthcare costs when an early amniotomy is performed as opposed to giving more PGE2 vaginal gel, for women undergoing IOL at term. Following an evening dose of PGE2 vaginal gel, 245 women with live singleton pregnancies, ≥37+0 weeks, were randomized into an amniotomy or repeat-PGE2 group. Healthcare costs were a secondary outcome measure, sourced from hospital finance systems and included staff costs, equipment and consumables, pharmacy, pathology, hotel services and business overheads. A decision analytic model, specifically a Markov chain, was developed to further investigate costs, and a Monte Carlo simulation was performed to confirm the robustness of these findings. Mean and median costs and cost differences between the two groups are reported, from the hospital perspective. The healthcare costs associated with IOL were available for all 245 trial participants. A 1000-patient cohort simulation demonstrated that performing an early amniotomy was associated with a cost-saving of $AUD289 ($AUD7094 vs $AUD7338) per woman induced, compared with administering more PGE2. Propagating the uncertainty through the model 10,000 times, early amniotomy was associated with a median cost savings of $AUD487 (IQR -$AUD573, +$AUD1498). After an initial dose of PGE2 vaginal gel, a policy of administering more PGE2 when the Modified Bishop's score is <7 was associated with increased healthcare costs compared with a policy of performing an amniotomy, if technically possible. Length of stay was the main driver of healthcare costs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vaginal ring delivery of selective progesterone receptor modulators for contraception

PubMed Central

Jensen, Jeffrey T.

2013-01-01

Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) are under development to address limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing, and therefore might improve the effectiveness of contraception. The principle contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1–2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6–7 ng/mL. PMID:23040126

A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

PubMed

Barnable, Patrick; Calenda, Giulia; Ouattara, Louise; Gettie, Agegnehu; Blanchard, James; Jean-Pierre, Ninochka; Kizima, Larisa; Rodríguez, Aixa; Abraham, Ciby; Menon, Radhika; Seidor, Samantha; Cooney, Michael L; Roberts, Kevin D; Sperling, Rhoda; Piatak, Michael; Lifson, Jeffrey D; Fernandez-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa; Teleshova, Natalia

2014-01-01

To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States.

PubMed

Mayer, K H; Peipert, J; Fleming, T; Fullem, A; Moench, T; Cu-Uvin, S; Bentley, M; Chesney, M; Rosenberg, Z

2001-02-01

BufferGel (ReProtect, LLC) is a vaginal gel with an acidic buffering action that was designed to prevent vaginal neutralization by semen. The purpose of this study was to evaluate the safety and tolerability of BufferGel (ReProtect, Limited Liability Company) applied vaginally either once or twice daily by 27 women who were at low risk for acquisition of human immunodeficiency virus (HIV). Participants initially used the product once daily for 14 days and then twice daily for 14 days; they underwent colposcopy before and after product exposure. BufferGel was well tolerated, although two-thirds of the participants reported at least 1 mild or moderate adverse experience. The most common adverse events were irritative genitourinary symptoms. Product use was discontinued after 3 adverse events. BufferGel was well tolerated in women at low risk for acquisition of HIV; toxicity was limited and occurred at frequencies similar to those in women who did not use any vaginal product and at levels lower than in women who used detergent-based microbicides.

Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS Study): A multicentre, randomised, placebo-controlled trial.

PubMed

Crowther, Caroline A; Ashwood, Pat; McPhee, Andrew J; Flenady, Vicki; Tran, Thach; Dodd, Jodie M; Robinson, Jeffrey S

2017-09-01

Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity. The withdrawal of progesterone, either actual or functional, is thought to be an antecedent to the onset of labour. There remains limited information on clinically relevant health outcomes as to whether vaginal progesterone may be of benefit for pregnant women with a history of a previous preterm birth, who are at high risk of a recurrence. Our primary aim was to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth reduced the risk and severity of respiratory distress syndrome in their infants, with secondary aims of examining the effects on other neonatal morbidities and maternal health and assessing the adverse effects of treatment. Women with a live singleton or twin pregnancy between 18 to <24 weeks' gestation and a history of prior preterm birth at less than 37 weeks' gestation in the preceding pregnancy, where labour occurred spontaneously or in association with cervical incompetence or following preterm prelabour rupture of the membranes, were eligible. Women were recruited from 39 Australian, New Zealand, and Canadian maternity hospitals and assigned by randomisation to vaginal progesterone pessaries (equivalent to 100 mg vaginal progesterone) (n = 398) or placebo (n = 389). Participants and investigators were masked to the treatment allocation. The primary outcome was respiratory distress syndrome and severity. Secondary outcomes were other respiratory morbidities; other adverse neonatal outcomes; adverse outcomes for the woman, especially related to preterm birth; and side effects of progesterone treatment. Data were analysed for all the 787 women (100%) randomised and their 799 infants. Most women used their allocated study treatment (740 women, 94.0%), with median use similar for both study groups (51.0 days, interquartile range [IQR] 28.0-69.0, in the progesterone

Comparison of Dapivirine Vaginal Gel and Film Formulation Pharmacokinetics and Pharmacodynamics (FAME 02B).

PubMed

Robinson, Jennifer A; Marzinke, Mark A; Bakshi, Rahul P; Fuchs, Edward J; Radebaugh, Christine L; Aung, Wutyi; Spiegel, Hans M L; Coleman, Jenell S; Rohan, Lisa C; Hendrix, Craig W

2017-04-01

While preexposure prophylaxis with oral tenofovir/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of vaginal gels and the potential for evolving drug resistance have led to development of vaginal film formulations and other antiretroviral drugs, respectively, including the non-nucleoside reverse transcriptase inhibitor dapivirine. In this two-arm crossover study of a novel fast-dissolving dapivirine film and a previously studied semisolid dapivirine gel, 10 healthy women received a single 1.25 mg vaginal dose of each study product; one withdrew after the first dose. Clinical, pharmacokinetic, and antiviral pharmacodynamic assessments (ex vivo HIV-BaL challenge of tissue explants) were performed over 168 h postdose. Six of ten participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or adverse events attributed to study products. There were no statistically significant differences in plasma, cervicovaginal fluid (CVF), or cervical tissue dapivirine concentrations between the gel and film (all p > .05). CVF dapivirine concentrations were 1.5 and 6 log 10 greater than tissue and plasma concentrations, respectively (p < .001). Both film and gel demonstrated reduced cervical tissue infectivity after ex vivo HIV challenge 5 h postdose, compared to baseline and 72-h postdose biopsies (p < .05 for gel, p = .06 for film). There was no difference in ex vivo explant HIV challenge between gel and film. The dapivirine film and gel performed similarly in terms of tolerability, pharmacokinetics, and antiviral effect. Dapivirine film may provide an alternative to pharmacokinetically comparable dapivirine gel formulations. Effectiveness remains to be tested.

Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data.

PubMed

Romero, R; Conde-Agudelo, A; El-Refaie, W; Rode, L; Brizot, M L; Cetingoz, E; Serra, V; Da Fonseca, E; Abdelhafez, M S; Tabor, A; Perales, A; Hassan, S S; Nicolaides, K H

2017-03-01

To assess the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal morbidity and mortality in asymptomatic women with a twin gestation and a sonographic short cervix (cervical length ≤ 25 mm) in the mid-trimester. This was an updated systematic review and meta-analysis of individual patient data (IPD) from randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a twin gestation and a mid-trimester sonographic cervical length ≤ 25 mm. MEDLINE, EMBASE, POPLINE, CINAHL and LILACS (all from inception to 31 December 2016), the Cochrane Central Register of Controlled Trials, Research Registers of ongoing trials, Google Scholar, conference proceedings and reference lists of identified studies were searched. The primary outcome measure was preterm birth < 33 weeks' gestation. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. IPD were available for 303 women (159 assigned to vaginal progesterone and 144 assigned to placebo/no treatment) and their 606 fetuses/infants from six randomized controlled trials. One study, which included women with a cervical length between 20 and 25 mm, provided 74% of the total sample size of the IPD meta-analysis. Vaginal progesterone, compared with placebo/no treatment, was associated with a statistically significant reduction in the risk of preterm birth < 33 weeks' gestation (31.4% vs 43.1%; RR, 0.69 (95% CI, 0.51-0.93); moderate-quality evidence). Moreover, vaginal progesterone administration was associated with a significant decrease in the risk of preterm birth < 35, < 34, < 32 and < 30 weeks' gestation (RRs ranging from 0.47 to 0.83), neonatal death (RR, 0.53 (95% CI, 0.35-0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56-0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34-0.98)), use of mechanical

Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

PubMed

Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

2012-01-01

A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

VAGINAL PROGESTERONE IN WOMEN WITH AN ASYMPTOMATIC SONOGRAPHIC SHORT CERVIX IN THE MIDTRIMESTER DECREASES PRETERM DELIVERY AND NEONATAL MORBIDITY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF INDIVIDUAL PATIENT DATA

PubMed Central

ROMERO, Roberto; NICOLAIDES, Kypros; CONDE-AGUDELO, Agustin; TABOR, Ann; O’BRIEN, John M.; CETINGOZ, Elcin; DA FONSECA, Eduardo; CREASY, George; KLEIN, Katharina; RODE, Line; SOMA-PILLAY, Priya; FUSEY, Shalini; CAM, Cetin; ALFIREVIC, Zarko; HASSAN, Sonia S.

2012-01-01

OBJECTIVE To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix in the mid-trimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN Individual patient data meta-analysis of randomized controlled trials. RESULTS Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (RR 0.58, 95% CI 0.42–0.80), <35 weeks (RR 0.69, 95% CI 0.55–0.88) and <28 weeks (RR 0.50, 95% CI 0.30–0.81), respiratory distress syndrome (RR 0.48, 95% CI 0.30–0.76), composite neonatal morbidity and mortality (RR 0.57, 95% CI 0.40–0.81), birth weight <1500 g (RR 0.55, 95% CI 0.38–0.80), admission to NICU (RR 0.75, 95% CI 0.59–0.94), and requirement for mechanical ventilation (RR 0.66, 95% CI 0.44–0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality. PMID:22284156

Use of lubricant gel to shorten the second stage of labor during vaginal delivery.

PubMed

Aquino, Carmen Imma; Saccone, Gabriele; Troisi, Jacopo; Zullo, Fulvio; Guida, Maurizio; Berghella, Vincenzo

2018-05-27

Vaginal application of lubricant during labor has been studied to shorten the length of the second stage of labor. To evaluate whether vaginal application of lubricant shortens the second stage of labor. Electronic databases were searched from their inception until February 2018. No restrictions for language or geographic location were applied. Randomized controlled trials (RCTs) comparing the use of lubricant of the vaginal canal (ie intervention group) with a control group (ie no lubricant) in pregnant women with singleton gestation and cephalic presentation undergoing spontaneous vaginal delivery at term. Trials on other interventions that might impact second stage of labor (pushing methods, perineal massage, Ritgen's maneuver, etc.) were not included. All analyses were done using an intention-to-treat approach. The primary outcome was the length of the second stage of labor. Pooled analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of mean difference (MD) with 95% confidence interval (CI). Three RCTs including 512 women evaluating the effect of lubricant application during labor were included in the meta-analysis. All trials included pregnant women with singleton gestations in cephalic presentation at term undergoing spontaneous vaginal delivery. One trial included only nulliparous women, while the other two included both nulliparous and multiparous women. Lubricant application started in the first stage before the active phase of labor, and was done intermittently by the midwife or the physician. A sterile gel was applied into the vaginal canal manually or with an applicator. All trials used water-soluble gel. The quantity of gel used was about 2-5 ml for each vaginal examination. There were no statistically significant differences, comparing women who received lubricant gel during labor with those who did not, in the lengths of second stage of labor (MD -7.11 minutes, 95% CI -15

Comparison of Dapivirine Vaginal Gel and Film Formulation Pharmacokinetics and Pharmacodynamics (FAME 02B)

PubMed Central

Marzinke, Mark A.; Bakshi, Rahul P.; Fuchs, Edward J.; Radebaugh, Christine L.; Aung, Wutyi; Spiegel, Hans M.L.; Coleman, Jenell S.; Rohan, Lisa C.; Hendrix, Craig W.

2017-01-01

Abstract While preexposure prophylaxis with oral tenofovir/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of vaginal gels and the potential for evolving drug resistance have led to development of vaginal film formulations and other antiretroviral drugs, respectively, including the non-nucleoside reverse transcriptase inhibitor dapivirine. In this two-arm crossover study of a novel fast-dissolving dapivirine film and a previously studied semisolid dapivirine gel, 10 healthy women received a single 1.25 mg vaginal dose of each study product; one withdrew after the first dose. Clinical, pharmacokinetic, and antiviral pharmacodynamic assessments (ex vivo HIV-BaL challenge of tissue explants) were performed over 168 h postdose. Six of ten participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or adverse events attributed to study products. There were no statistically significant differences in plasma, cervicovaginal fluid (CVF), or cervical tissue dapivirine concentrations between the gel and film (all p > .05). CVF dapivirine concentrations were 1.5 and 6 log10 greater than tissue and plasma concentrations, respectively (p < .001). Both film and gel demonstrated reduced cervical tissue infectivity after ex vivo HIV challenge 5 h postdose, compared to baseline and 72-h postdose biopsies (p < .05 for gel, p = .06 for film). There was no difference in ex vivo explant HIV challenge between gel and film. The dapivirine film and gel performed similarly in terms of tolerability, pharmacokinetics, and antiviral effect. Dapivirine film may provide an alternative to pharmacokinetically comparable dapivirine gel formulations. Effectiveness remains to be tested. PMID:27809557

Highly efficient treatment of aerobic vaginitis with simple acidic buffered gels: The importance of pH and buffers on the microenvironment of vaginas.

PubMed

Sun, Xiaodong; Qiu, Haiying; Jin, Yiguang

2017-06-15

Aerobic vaginitis (AV) leads to uterus deep infection or preterm birth. Antibacterial agents are not optimal therapeutics of AV. Here, we report a series of temperature-sensitive in situ forming acidic buffered gels for topical treatment of AV, involving lactate, acetate, and citrate gels at pH 3.5, 5.0, and 6.5. AV rat models were prepared following vaginal infection with Staphylococcus aureus and Escherichia coli. In vitro/in vivo studies of the buffered gels were performed compared with ofloxacin gels and blank gels. All the buffered gels showed the lower in vitro antibacterial activities than ofloxacin gels but the better in vivo anti-S. aureus effects and similar anti-E. coli effects. The buffered gels improved Lactobacillus growth in the vaginas. Both the healthy rat vaginal pH and the pH of rat vaginas treated with the buffered gels were about 6.5 though the AV rat models or ones treated with ofloxacin gels still remained at the high pH more than 7.0. After treatments with the buffered gels, the vaginal smears changed to a clean state nearly without aerobic bacteria, the vaginal tissues were refreshed, and the immunoreactions were downregulated. The acidic buffered gels bring rapid decrease of local vaginal pH, high antibacterial activities, improvement of probiotics, and alleviation of inflammation. They are simple, highly efficient, and safe anti-AV formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

PubMed

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Zydowsky, Thomas M; Robbiani, Melissa

2012-11-01

Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

Progesterone to prevent spontaneous preterm birth

PubMed Central

Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

2014-01-01

Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth <33 weeks of gestation, 12 patients with a short cervix would need to be treated. Vaginal progesterone reduces the rate of spontaneous preterm birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

A Single Dose of a MIV-150/Zinc Acetate Gel Provides 24 h of Protection Against Vaginal Simian Human Immunodeficiency Virus Reverse Transcriptase Infection, with More Limited Protection Rectally 8–24 h After Gel Use

PubMed Central

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J.; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, José A.; Zydowsky, Thomas M.

2012-01-01

Abstract Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4–24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8–24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8–24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure. PMID:22737981

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

PubMed

Norman, Jane E; Mackenzie, Fiona; Owen, Philip; Mactier, Helen; Hanretty, Kevin; Cooper, Sarah; Calder, Andrew; Mires, Gary; Danielian, Peter; Sturgiss, Stephen; MacLennan, Graeme; Tydeman, Graham; Thornton, Steven; Martin, Bill; Thornton, James G; Neilson, James P; Norrie, John

2009-06-13

Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51). Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. Chief Scientist Office of the Scottish Government Health Directorate.

Transdermal absorption of natural progesterone from alcoholic gel formulations with hydrophilic surfactant.

PubMed

Matsui, Rakan; Ueda, Osamu; Uchida, Shinya; Namiki, Noriyuki

2015-06-01

The aim of this study was to evaluate the in vitro skin permeation and in vivo transdermal absorption of natural progesterone (Prog) from alcoholic gel-based transdermal formulations containing Prog dissolved stably at a concentration of 3%. 3% Prog dissolved gel formulations were prepared containing with water, ethanol, 1,3-butylene glycol, carboxyvinylpolymer, diisopropanolamine, polyoxyethylene (2) oleylether and benzyl alcohol. The gel formulations added different hydrophilic surfactants and isopropyl myristate or propylene glycol dicaprylate (PGDC) as oily solvents were applied in vitro permeation study through excised rat skin on unocclusive condition. The gel formulations added polyoxyethylene (20) oleylether (Oleth-20) as hydrophilic surfactant and PGDC were applied in vivo single- and repeated-dose transdermal absorption study of rat on unocclusive condition. The results of evaluation of the gel formulations by an in vitro skin permeation study revealed a high flux of Prog from the formulation containing Oleth-20 and Oleth-20 with PGDC. The results of single and repeated in vivo transdermal absorption studies confirmed that good plasma levels of Prog were achieved and maintained by Oleth-20 and PGDC containing gel formulation. The Oleth-20 and PGDC containing ethanolic gel formulation seemed to have the ability to maintain a high activity of Prog and high diffusivity or solubility of Prog in the epidermis on the practical formulation application.

Effects of Reproductive Hormones on Experimental Vaginal Candidiasis

PubMed Central

Fidel, Paul L.; Cutright, Jessica; Steele, Chad

2000-01-01

Vulvovaginal candidiasis (VVC) is an opportunistic mucosal infection caused by Candida albicans that affects large numbers of otherwise healthy women of childbearing age. Acute episodes of VVC often occur during pregnancy and during the luteal phase of the menstrual cycle, when levels of progesterone and estrogen are elevated. Although estrogen-dependent experimental rodent models of C. albicans vaginal infection are used for many applications, the role of reproductive hormones and/or their limits in the acquisition of vaginal candidiasis remain unclear. This study examined the effects of estrogen and progesterone on several aspects of an experimental infection together with relative cell-mediated immune responses. Results showed that while decreasing estrogen concentrations eventually influenced infection-induced vaginal titers of C. albicans and rates of infection in inoculated animals, the experimental infection could not be achieved in mice treated with various concentrations of progesterone alone. Furthermore, progesterone had no effect on (i) the induction and persistence of the infection in the presence of estrogen, (ii) delayed-type hypersensitivity in primary-infected mice, or (iii) the partial protection from a secondary vaginal infection under pseudoestrus conditions. Other results with estrogen showed that a persistent infection could be established with a wide range of C. albicans inocula under supraphysiologic and near-physiologic (at estrus) concentrations of estrogen and that vaginal fungus titers or rates of infection were similar if pseudoestrus was initiated several days before or after inoculation. However, the pseudoestrus state had to be maintained for the infection to persist. Finally, estrogen was found to reduce the ability of vaginal epithelial cells to inhibit the growth of C. albicans. These results suggest that estrogen, but not progesterone, is an important factor in hormone-associated susceptibility to C. albicans vaginitis. PMID

Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.

PubMed

Sokal, David C; Karim, Quarraisha Abdool; Sibeko, Sengeziwe; Yende-Zuma, Nonhlanhla; Mansoor, Leila E; Baxter, Cheryl; Grobler, Anneke; Frolich, Janet; Kharsany, Ayesha Bm; Miya, Nomsa; Mlisana, Koleka; Maarshalk, Silvia; Karim, Salim S Abdool

2013-01-01

Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters. In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated. Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group. No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.

Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

PubMed

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

Beneficial effects of a Coriolus versicolor-based vaginal gel on cervical epithelization, vaginal microbiota and vaginal health: a pilot study in asymptomatic women.

PubMed

Palacios, Santiago; Losa, Fernando; Dexeus, Damián; Cortés, Javier

2017-03-16

To assess the effect of a 12-day treatment using a vaginal gel based on niosomes containing hyaluronic acid, ß-glucan, alpha-glucan oligosaccharide, Coriolus versicolor, Asian centella, Azadirachta indica and Aloe vera on vaginal microbiota, cervical epithelization and vaginal health. Open-label, prospective pilot study conducted in asymptomatic women in daily practice. Cervical epithelization was evaluated by colposcopy using an ectopy epithelization score (from 5: no ectopy to 1: severe ectopy and bleeding), vaginal microbiota using the VaginaStatus-Diagnostic test (Instiüt für Mikroökologie, Herborn, Germany) and further rated by the investigator using a 5-point Liker scale (from 5: normal to 1: very severe deterioration in which all evaluated species were altered), and vaginal health using the Vaginal Health Index. In 21 women, a positive effect to improve epithelization of the cervical mucosa, with a mean score of 4.42 at the final visit as compared to 3.09 at baseline (P < 0.0001) (43% improvement). In 10 women, there was a trend of improving of vaginal microbiota status, with a mean score of 4.0 at the final visit vs. 3.3 at baseline (P = NS) (21.2% improvement). In 11 women, the Vaginal Health Index increased from 19.0 at baseline to 22.3 at the final visit (P = 0.007). The concentration of Lactobacillus spp. increased 54.5% of women and pH decreased from 4.32 to 4.09. These encouraging preliminary results provide the basis for designing a randomized controlled study, and for potential use in human papilloma virus infection. ISRCTN77955077 . Registration date: February 15, 2017. Retrospectively registered.

Persistent Genital Hyperinnervation Following Progesterone Administration to Adolescent Female Rats1

PubMed Central

Liao, Zhaohui; Smith, Peter G.

2014-01-01

ABSTRACT Provoked vestibulodynia, a female pelvic pain syndrome affecting substantial numbers of women, is characterized by genital hypersensitivity and sensory hyperinnervation. Previous studies have shown that the risk of developing provoked vestibulodynia is markedly elevated following adolescent use of oral contraceptives with high progesterone content. We hypothesized that progesterone, a steroid hormone with known neurotropic properties, may alter genital innervation through direct or indirect actions. Female Sprague Dawley rats received progesterone (20 mg/kg subcutaneously) from Days 20–27; tissue was removed for analysis in some rats on Day 28, while others were ovariectomized on Day 43 and infused for 7 days with vehicle or 17beta estradiol. Progesterone resulted in overall increases in vaginal innervation at both Day 28 and 50 due to proliferation of peptidergic sensory and sympathetic (but not parasympathetic) axons. Estradiol reduced innervation in progesterone-treated and untreated groups. To assess the mechanisms of sensory hyperinnervation, we cultured dissociated dorsal root ganglion neurons and found that progesterone increases neurite outgrowth by small unmyelinated (but not myelinated) sensory neurons, it was receptor mediated, and it was nonadditive with NGF. Pretreatment of ganglion with progesterone also increased neurite outgrowth in response to vaginal target explants. However, pretreatment of vaginal target with progesterone did not improve outgrowth. We conclude that adolescent progesterone exposure may contribute to provoked vestibulodynia by eliciting persistent genital hyperinnervation via a direct effect on unmyelinated sensory nociceptor neurons and that estradiol, a well-documented therapeutic, may alleviate symptoms in part by reducing progesterone-induced sensory hyperinnervation. PMID:25359899

Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

PubMed Central

Keller, Marla J.; Carpenter, Colleen A.; Lo, Yungtai; Einstein, Mark H.; Liu, Congzhou; Fredricks, David N.; Herold, Betsy C.

2012-01-01

Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. Results The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Conclusions Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels

Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

PubMed

Nel, Annalene M; Coplan, Paul; van de Wijgert, Janneke H; Kapiga, Saidi H; von Mollendorf, Claire; Geubbels, Eveline; Vyankandondera, Joseph; Rees, Helen V; Masenga, Gileard; Kiwelu, Ireen; Moyes, Jocelyn; Smythe, Shanique C

2009-07-31

To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.

Silver Sucrose Octasulfate (IASOS™) as a Valid Active Ingredient into a Novel Vaginal Gel against Human Vaginal Pathogens: In Vitro Antimicrobial Activity Assessment

PubMed Central

Marianelli, Cinzia; Petrucci, Paola; Comelli, Maria Cristina; Calderini, Gabriella

2014-01-01

This in vitro study assessed the antimicrobial properties of a novel octasilver salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated from human clinical cases of symptomatic vaginal infections. In BHI and LAPT culture media, different ionic silver concentrations and different pHs were tested. IASOS exerted a strong antimicrobial activity towards all the pathogens tested in both culture media. The results demonstrated that salts and organic compounds present in the culture media influenced IASOS efficacy only to a moderate extent. Whereas comparable MBCs (Minimal Bactericidal Concentrations) were observed for G. vaginalis (10 mg/L Ag+), E. coli and E. aerogenes (25 mg/L Ag+) in both media, higher MBCs were found for S. aureus and S. agalactiae in LAPT cultures (50 mg/L Ag+ versus 25 mg/L Ag+). No minimal concentration totally inhibiting the growth of C. albicans was found. Nevertheless, in both media at the highest ionic silver concentrations (50–200 mg/L Ag+), a significant 34–52% drop in Candida growth was observed. pH differently affected the antimicrobial properties of IASOS against bacteria or yeasts; however, a stronger antimicrobial activity at pH higher than the physiological pH was generally observed. It can be therefore concluded that IASOS exerts a bactericidal action against all the tested bacteria and a clear fungistatic action against C. albicans. The antimicrobial activity of the whole vaginal gel SilSOS Femme further confirmed the antimicrobial activity of IASOS. Overall, our findings support IASOS as a valid active ingredient into a vaginal gel. PMID:24897299

Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

PubMed Central

Salem, Heba F

2010-01-01

The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r2 > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a Tmax of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC0-∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone. PMID:21187946

Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats.

PubMed

Salem, Heba F

2010-11-10

The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r² > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a T(max) of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC₀₋∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.

Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

PubMed

Nel, Annalene M; Coplan, Paul; Smythe, Shanique C; McCord, Karen; Mitchnick, Mark; Kaptur, Paulina E; Romano, Joseph

2010-11-01

To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) pg/mg. Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.

In vivo optical imaging of human vaginal gel thickness distributions with a probe-based, dual-modality instrument

NASA Astrophysics Data System (ADS)

Drake, Tyler K.; DeSoto, Michael G.; Peters, Jennifer J.; Henderson, Marcus H.; Thiele, Bonnie; Bishop, Tammy Sinclair; Murtha, Amy P.; Katz, David F.; Wax, Adam

2012-11-01

We used a probe-based dual-modality optical imaging instrument to measure in vivo coating thickness distributions of a gel distributed along the vaginal lumen, in a clinical study. The gel was a surrogate for one delivering an anti-HIV topical microbicide. Imaging data from Fourier-domain multiplexed low-coherence interferometry (mLCI) and fluorimetric measurements were compared to assess the feasibility and accuracy of mLCI in measuring in vivo gel coating thickness distributions. In each study session, 3.5 mL of Replens gel was inserted to the vaginal fornix while the participant was supine. The participant either: 1. remained supine (10 or 60 min) or 2. sat up (1 min), stood up (1 min), sat down (1 min) and returned to the supine position; net elapsed time was 10 or 60 min after which the gel distribution was imaged. Local coating thickness distributions were qualitatively and quantitatively similar. Here mLCI did not accurately measure thicker gel coatings (>0.8 mm), a limitation not seen with fluorimetry. However, mLCI is capable of measuring in vivo microbicide gel distributions with resolution on the order of 10 μm, without the need for exogenous contrast agents, and can accurately capture relevant summary coating measures in good agreement with fluorimetry.

SPL7013 Gel (VivaGel®) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans

PubMed Central

Price, Clare F.; Tyssen, David; Sonza, Secondo; Davie, Ashley; Evans, Sonya; Lewis, Gareth R.; Xia, Shirley; Spelman, Tim; Hodsman, Peter; Moench, Thomas R.; Humberstone, Andrew; Paull, Jeremy R.A.; Tachedjian, Gilda

2011-01-01

SPL7013 Gel (VivaGel®) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup™ pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest

The stimulation of the vaginal immune system with short-term administration of a vaginal gel containing fraction of Propionibacterium acnes, hyaluronic acid and polycarbophil is efficacious in vaginal infections dependent on disorders in the vaginal ecosystem.

PubMed

Melis, Gian Benedetto; Piras, Bruno; Marotto, Maria Francesca; Neri, Manuela; Corda, Valentina; Vallerino, Valerio; Saba, Alessandra; Lello, Stefano; Pilloni, Monica; Zedda, Pierina; Paoletti, Anna Maria; Mais, Valerio

2018-04-12

The vaginal immune system (VIS) is the first defense against antigens recognized as foreign. Substances capable of locally activating the VIS could be a valid strategy to treat vulvo-vaginal infections (VVI), caused by changes in the vaginal ecosystem, such as bacterial vaginosis (BV), vulvo-vaginal candidiasis (CA), and mixed vaginitis (MV). Bacterial lysates, obtained by crushing bacterial cultures, exert immuno-modulatory activities. The parietal fraction from Propionibacterium acnes is a patent of Depofarma (MoglianoVeneto, Italy). The preparation that associates such fraction to hyaluronic acid and polycarbophil is a registered trademark, commercially available in Italy as vaginal gel, Immunovag ® . The study aimed to evaluate whether a 5-day-treatment with Immunovag ® improves the symptoms and signs of VVI, in 60 women with Gardnerella vaginalis (GV), 154 with CA, 95 with MV, diagnosed with vulvar vaginal swab (VVS), and in 283 with BV, diagnosed with the Amsel criteria. At the end of the treatment (visit 2), the symptoms and signs of VVI disappeared in a significant number of subjects (χ 2 p < .02 vs pre-treatment) in all VVI groups, and their intensity was significantly (p < .0002) reduced in the subjects in which they were still present. Immunovag ® represents a valid treatment of VVI induced by changes in the vaginal ecosystem.

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard gel: a new formulation for "dual protection" contraception.

PubMed

Sitruk-Ware, Regine; Brache, Vivian; Maguire, Robin; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Montero, Juan Carlos; Salvatierra, Ana Maria; Phillips, David; Faundes, Anibal

2007-06-01

The study was conducted to assess levonorgestrel (LNG) serum levels achieved after a single administration of two different doses of Carraguard vaginal gel containing LNG (CARRA/LNG), designed for use as microbicide and contraceptive for potential dual protection. This was a randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled at two centers. Each subject received a single vaginal administration of CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on Days 10-12 of the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h after administration and for the following 7 days. LH and progesterone (for a preliminary evaluation of effect on the ovarian function) as well as SHBG were measured in the daily samples. Serum LNG maximum concentrations (Cmax) were 14.1+/-2.1 and 11.7+/-2.7 nmol/L and Tmax was 12.0 and 6.0 h for the low and high dose, respectively, with large intersubject variability within the first 48 h. Mean levels at 96 h were 10% of Cmax. Differences in AUC between both doses were not statistically significant. SHBG levels decreased approximately 25% by Day 4 after administration. Luteal activity was observed in 3/6 and 5/6 of the subjects in the low- and high-dose group, respectively. This study demonstrates that the CARRA/LNG gel can sustain elevated serum levels of the contraceptive steroid for up to 96 h after a single application. The serum levels attained with the 0.75-mg formulation are in the range expected to perturb the ovulatory process as observed in some subjects. The lack of correlation between the administered dose and serum concentrations of the steroid may be related to a rate-limiting absorption of LNG from the vaginal mucosa. The results reported here suggest that the CARRA/LNG formulation has good potential to become a dual-protection method, possibly preventing conception and sexually transmitted infections.

Vaginal drug distribution modeling.

PubMed

Katz, David F; Yuan, Andrew; Gao, Yajing

2015-09-15

This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

PubMed Central

Chen, Daquan; Sun, Kaoxiang; Mu, Hongjie; Tang, Mingtan; Liang, Rongcai; Wang, Aiping; Zhou, Shasha; Sun, Haijun; Zhao, Feng; Yao, Jianwen; Liu, Wanhui

2012-01-01

Background In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration. Methods The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment. Results A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0). Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0. Conclusion This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery. PMID:22679372

Thermosensitive bioadhesive gels for the vaginal delivery of sildenafil citrate: in vitro characterization and clinical evaluation in women using clomiphene citrate for induction of ovulation.

PubMed

Soliman, Ghareb M; Fetih, Gihan; Abbas, Ahmed M

2017-03-01

The objective of this study is to develop and characterize in situ thermosensitive gels for the vaginal administration of sildenafil as a potential treatment of endometrial thinning occurring as a result of using clomiphene citrate for ovulation induction in women with type II eugonadotrophic anovulation. While sildenafil has shown promising results in the treatment of infertility in women, the lack of vaginal pharmaceutical preparation and the side effects associated with oral sildenafil limit its clinical effectiveness. Sildenafil citrate in situ forming gels were prepared using different grades of Pluronic ® (PF-68 and PF-127). Mucoadhesive polymers as sodium alginate and hydroxyethyl cellulose were added to the gels in different concentrations and the effect on gel properties was studied. The formulations were evaluated in terms of viscosity, gelation temperature (T sol-gel ), mucoadhesion properties, and in vitro drug release characteristics. Selected formulations were evaluated in women with clomiphene citrate failure due to thin endometrium (Clinicaltrial.gov identifier NCT02766725). The T sol-gel decreased with increasing PF-127 concentration and it was modulated by addition of PF-68 to be within the acceptable range of 28-37 °C. Increasing Pluronic® concentration increased gel viscosity and mucoadhesive force but decreased drug release rate. Clinical results showed that the in situ sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow with no reported side effects. Further, these results were achieved at lower frequency and duration of drug administration. Sildenafil thermosensitive vaginal gels might result in improved potential of pregnancy in anovulatory patients with clomiphene citrate failure due to thin endometrium.

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception

PubMed Central

Sitruk-Ware, R; Brache, V; Maguire, R; Croxatto, H; Kumar, N; Kumar, S; Montero, JC; Salvatierra, AM; Phillips, D; Faundes, A

2007-01-01

Objective: The study was conducted to assess levonorgestrel (LNG) serum levels achieved after a single administration of two different doses of Carraguard vaginal gel containing LNG (CARRA/LNG), designed for use as microbicide and contraceptive for potential dual-protection. Materials and methods: This was a randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled at two centers. Each subject received a single vaginal administration of CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on day 10-12 of the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h after administration and for the following seven days. LH and progesterone (for a preliminary evaluation of effect on the ovarian function) as well as SHBG were measured in the daily samples. Results: Serum LNG maximum concentrations (Cmax) were 14.1 ± 5.1 and 11.7 ± 6.5 nmol/L and Tmax was 12.0 and 6.0 h for the low and high dose, respectively, with large intersubject variability within the first 48 h. Mean levels at 96 h were 10% of Cmax. Differences in AUC between both doses were not statistically significant. SHBG levels decreased approximately 25% by day 4 after administration. Luteal activity was observed in 3/6 and 5/6 of the subjects in the low and high dose group, respectively. Conclusion: This study demonstrates that the CARRA/LNG gel can sustain elevated serum levels of the contraceptive steroid for up to 96 h after a single application. The serum levels attained with the 0.75 mg formulation are in the range expected to perturb the ovulatory process as observed in some subjects. The lack of correlation between the administered dose and serum concentrations of the steroid may be related to a rate-limiting absorption of LNG from the vaginal mucosa. The results reported here suggest that the CARRA/LNG formulation has good potential to become a dual-protection method, possibly preventing conception and sexually transmitted infections. PMID:17519152

Pharmacokinetics of Lidocaine and Its Metabolites Following Vaginal Administration of Lidocaine Gel to Healthy Female Subjects

PubMed Central

Kushner, Harvey; Richardson, Elaine; Mize, Amy; Mayer, Philip

2016-01-01

Abstract Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single‐dose and multiple‐dose studies in healthy young adult women. Lidocaine doses of 2.5%, 5%, and 10% (w/w) were administered, and parent drug and metabolites monoethylglycinexylidide and glycinexylidide were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose‐proportional manner, and there was little systemic accumulation. Plasma concentrations were 10‐ to 20‐fold lower than concentrations obtained after administration of intravenous lidocaine used to treat arrhythmic activity, thus demonstrating a wide safety margin for a vaginal lidocaine product. PMID:27297519

Addition of adjuvant progesterone to physical-exam-indicated cervical cerclage to prevent preterm birth.

PubMed

Jung, Eun Young; Oh, Kyung Joon; Hong, Joon-Seok; Han, Bo Ryoung; Joo, Jung Kyung

2016-12-01

The aim of this study was to assess the effect of vaginal progesterone as an adjuvant therapy to physical-exam-indicated cervical cerclage (PEICC). This retrospective cohort study included 53 consecutive singleton women who underwent PEICC because of acute cervical insufficiency at 17-24 gestational weeks. The study population was divided into two groups: the adjuvant progesterone group (n = 18) and the non-adjuvant group (n = 35). A 200-mg dose of vaginal micronized natural progesterone was administered after cerclage in the adjuvant progesterone group. Primary outcome measure was spontaneous preterm birth (SPTB) at <36 weeks. The SPTB rate at <36 weeks in the adjuvant group was significantly lower than in the non-adjuvant group (17% vs 51%, P < 0.05). Adjuvant progesterone therapy was significantly associated with a reduction in SPTB at <36 weeks (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.69, P < 0.05) even after adjusting for known covariates, including a visible membrane size of ≥4 cm, gestational age, prior SPTB, and use of amnioreduction. The frequency of SPTB at <32 weeks, birthweight < 2500 g, and neonatal intensive care unit admission was significantly lower in the adjuvant progesterone group than in the non-adjuvant group (P < 0.05 for all). Adjuvant vaginal progesterone therapy with PEICC was associated with reductions in SPTB, low birthweight, and neonatal intensive care unit admission. © 2016 Japan Society of Obstetrics and Gynecology.

In vitro inhibition of human papillomavirus following use of a carrageenan-containing vaginal gel.

PubMed

Novetsky, Akiva P; Keller, Marla J; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L; Xue, Xiaonan; Strickler, Howard D; Fernández-Romero, José A; Burk, Robert; Einstein, Mark H

2016-11-01

To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Sexually active US women between 19 and 35years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8-12h after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8-12h after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8-12h, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vitro Inhibition of Human Papillomavirus Following Use of a Carrageenan-Containing Vaginal Gel

PubMed Central

Novetsky, Akiva P.; Keller, Marla J.; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L.; Xue, Xiaonan; Strickler, Howard D.; Fernández-Romero, José A.; Burk, Robert; Einstein, Mark H.

2016-01-01

Objective To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Methods Sexually active US women between 19–35 years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8–12 hours after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8–12 hours after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Results Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8–12 hours, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). Conclusions This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. PMID:27625046

An evaluation of prostaglandin E2 vaginal gel use in practice.

PubMed

Taylor, S J; Peat, J K; Armour, C L

1999-08-01

The purpose of this study was to investigate the effectiveness of prostaglandin E2 vaginal gel as used in practice, rather than its efficacy as assessed in randomised, controlled, clinical trials. This product is used to ripen the cervix prior to induction of labour, sometimes making unnecessary the use of the standard treatment for induction, artificial rupture of the membranes (ARM) plus oxytocin. In this study, effectiveness of the gel was assessed in terms of changes in mode of delivery, and in particular the risk of Caesarean section. An historical control was used and the risk of Caesarean section for women induced in the 1990/91 (before the introduction of the gel) was compared with that for women induced in 1992/93 (after the introduction of the gel). Maternal characteristics which may have been different in the two groups and factors which might influence the risk of Caesarean section were controlled for statistically using logistic regression, thus reducing any bias towards one group. After adjusting for the factors which had a significant effect on the process of labour from induction to birth, it was found that the risk of Caesarean section was not significantly lower in the 1992/93-time period, when the gel was in regular use, from that in the 2 years prior to its introduction (Odds ratio 1.09, CI95% 0.88, 1.36). Following the introduction of PGE2 gel, no difference in effectiveness, as measured in terms of mode of delivery, was detected in this study of practice, which included patients with more complex obstetric problems.

Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan.

PubMed

Cevher, Erdal; Sensoy, Demet; Taha, Mohamed A M; Araman, Ahmet

2008-01-01

The aim of this study was to design and evaluate of mucoadhesive gel formulations for the vaginal application of clomiphene citrate (CLM) for local treatment of human papilloma virus (HPV) infections. Chitosan (CHI) and polycarbophil (PC) were covalently modified using the thioglycolic acid and L-cysteine, respectively. The formation of thiol conjugates of chitosan (CHI-TG) and polycarbophil (PC-CYS) were confirmed by FT-IR analysis and PC-CYS and CHI-TG were found to have 148.42 +/- 4.16 and 41.17 +/- 2.34 micromol of thiol groups per gram of polymer, respectively. One percent CLM gels were prepared by combination of various concentrations of PC and CHI with thiolated conjugates of these polymers. Hardness, compressibility, elasticity, adhesiveness and cohesiveness of the gels were measured by Texture profile analysis and the vaginal mucoadhesion was investigated by mucoadhesion test. The increasing in the amount of the thiol conjugates was found to enhance the elasticity, cohesiveness, adhesiveness and mucoadhesion of the gel formulations but not their hardness and compressibility when compared to gels prepared using their respective parent formulations. Slower release rate of CLM from gels was achieved when the polymer concentrations were increased in the gel formulations. PC and its thiol conjugate were found to prolong the release of CLM longer than 70 h unlike gel formulations prepared using CHI and its thiol conjugate which were able to release CLM up to 12 h. Stability of CLM was preserved during the 3 month stability analysis under controlled room temperature and accelerated conditions.

Progesterone and estradiol plasma levels in neonatally irradiated cycling rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freud, A.; Sod-Moriah, U.A.

1990-01-01

Female rats which were exposed to a single low dose of gamma irradiation (6R or 15R) at the age of 8 days produce smaller litters when mature than untreated controls. The possibility that the impaired fertility resulted from altered ovarian activity as reflected by changes in plasma levels of progesterone or estardiol was investigated. Plasma levels of both steroids were determined throughout the day of proestrus. Progesterone level was also determined in 6R animals on the day of weaning. The maturity of such irradiated rats was assessed by observing the time of vaginal opening. The results indicated that the preovulatorymore » peak of progesterone was delayed in the 6R rats whereas in the 15R group its levels were significantly lower. On the other hand no differences in estradiol plasma levels were noticed between the groups. The higher level of progesterone in the 6R animals was not evident on the day of weaning and was even in both groups, but vaginal opening in the irradiated rats was significantly delayed. The elevated level of progesterone might be responsible, among other endocrine changes, for the lower fertility of neonatally irradiated mature female rats.« less

Effect of sexual intercourse on the absorption of levonorgestrel after vaginal administration of 0.75 mg in Carraguard® gel: a randomized, cross-over, pharmacokinetic study☆

PubMed Central

Brache, Vivian; Croxatto, Horacio; Kumar, Narender; Sitruk-Ware, Regine; Cochón, Leila; Schiappacasse, Veronica; Sivin, Irving; Muñoz, Carla; Maguire, Robin; Faundes, Anibal

2010-01-01

Background The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard® gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner. Study Design This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application. In each study arm, each woman received a single application of Carra/LNG gel (0.75 mg in 4 mL gel) followed by serial blood samples taken at 0, 1, 2, 4, 8, 24 and 48 h after gel application for LNG measurements. In the intercourse arm, LNG was measured in blood samples taken from the male partner before intercourse and at 4, 8 and 24 h after gel application in the female partner. Results Time concentration curves for serum LNG levels showed a mean Cmax of 7.8±5.5 and 8.3±5.7 nmol/L, a mean Tmax of 6.2±5.9 and 7.5±5.7, and comparable area under the curve for the intercourse and abstinence arm, respectively. Pharmacokinetic parameters presented large variability between subjects, but excellent reproducibility within each subject. LNG was undetectable in 10 out of 12 male partners. Conclusion Sexual intercourse does not appear to interfere with vaginal absorption of LNG after application of a Carra/LNG gel. A vaginal pre-coital contraceptive gel is feasible. PMID:19135574

Development of a novel synergistic thermosensitive gel for vaginal candidiasis: an in vitro, in vivo evaluation.

PubMed

Mirza, Mohd Aamir; Ahmad, Sayeed; Mallick, Md Nasar; Manzoor, Nikhat; Talegaonkar, Sushama; Iqbal, Zeenat

2013-03-01

The singular aim of the proposed work is the development of a synergistic thermosensitive gel for vaginal application in subjects prone to recurrent vaginal candidiasis and other microbial infections. The dual loading of Itraconazole and tea tree oil in a single formulation seems promising as it would elaborate the microbial coverage. Despite being low solubility of Itraconazole in tea tree oil, a homogeneous, transparent and stable solution of both was created by co-solvency using chloroform. Complete removal of chloroform was authenticated by GC-MS and the oil solution was used in the development of nanoemulsion which was further translated into a gel bearing thermosensitive properties. In vitro analyses (MTT assay, viscosity measurement, mucoadhesion, ex vivo permeation, etc.) and in vivo studies (bioadhesion, irritation potential and fungal clearance kinetics in rat model) of final formulation were carried out to establish its potential for further clinical evaluation. Copyright © 2012 Elsevier B.V. All rights reserved.

Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by Ureaplasma urealyticum during pregnancy - Results of a pilot study.

PubMed

Koucký, Michal; Malíčková, Karin; Cindrová-Davies, Tereza; Smíšek, Jan; Vráblíková, Hana; Černý, Andrej; Šimják, Patrik; Slováčková, Miroslava; Pařízek, Antonín; Zima, Tomáš

2016-08-01

Preterm birth is a leading cause of perinatal mortality and morbidity. Heavy cervicovaginal Ureaplasma colonization is thought to play a role in the pathogenesis of preterm birth. The administration of vaginal progesterone has been shown to reduce the incidence of preterm birth in women with short cervical length. Steroid hormones seem to modulate the presence of microorganisms in the vagina. The aim of this study was to assess whether the treatment with vaginal progesterone could reduce the incidence of preterm birth and cervicovaginal colonization by Ureaplasma urealyticum in a cohort of pregnant women with threatened preterm labor. A cohort of 63 females who presented with regular contractions and/or short cervical length between 24-32 weeks of gestation were recruited into a prospective study. 70% of patients had been treated with vaginal progesterone prior to recruitment and these patients continued with the treatment until birth. All patients were tested for the presence of cervicovaginal Ureaplasma urealyticum colonization at admission. The primary endpoint was preterm birth before 37 weeks. The incidence of preterm delivery was significantly increased in patients who tested positive for Ureaplasma urealyticum. Prolonged vaginal progesterone administration was associated with less frequent cervicovaginal colonization by U. urealyticum. Cervicovaginal colonization by U. urealyticum and absence of progesterone treatment were identified as two independent risk factors for preterm delivery. Our results demonstrate the beneficial effects of progesterone administration in reducing the incidence of cervicovaginal colonization by Ureaplasma urealyticum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial.

PubMed

Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

2015-07-01

The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group.

Safety of a progesterone-releasing intravaginal device as assessed from vaginal mucosal integrity and indicators of systemic inflammation in postpartum dairy cows

PubMed Central

Walsh, Robert B.; LeBlanc, Stephen J.; Vernooy, Erin; Leslie, Kenneth E.

2008-01-01

A clinical trial was conducted to investigate the animal safety of a progesterone-releasing intravaginal device (PRID). Anestrus cows at a mean of 63 ± 3.5 d in milk were randomly assigned to an ovulation-synchronization protocol that included placement of either a PRID or a placebo intravaginal device (PID) or no such treatment. At enrolment and at device removal 7 d later, blood samples were collected. The outcomes of interest included the vaginal reaction to the device, the vaginal mucosal integrity, and the results of bacterial culture of swabs of the vaginal mucosa. In addition, the leukocyte and haptoglobin responses were measured. Although only 5% of the PRID-treated animals compared with 19% of the PID-treated animals had a copious purulent vaginal discharge at the time of device removal, there was no significant difference in the proportions; furthermore, there was no evidence of vaginal mucosal damage associated with either device. The total blood leukocyte count was significantly lower in both the PRID-treated cows and the PID-treated cows after device removal compared with the start of treatment (P < 0.05) and compared with no treatment (P < 0.001); there was no difference in leukocyte response between the 2 device-treated groups. The decrease in leukocyte count was attributed to a significant reduction in the numbers of circulating neutrophils and lymphocytes, a pattern consistent with the luteal phase of the bovine estrus cycle. There was no significant difference in the circulating haptoglobin concentration between the 3 groups of cows. Culture revealed commensal bacterial growth in the vagina of all the cows. PMID:18214161

Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women.

PubMed

Smith, Gordon I; Reeds, Dominic N; Okunade, Adewole L; Patterson, Bruce W; Mittendorfer, Bettina

2014-07-01

Sexual dimorphism in plasma triglyceride (TG) metabolism is well established but it is unclear to what extent it is driven by differences in the sex hormone milieu. RESULTS from previous studies evaluating the effects of sex steroids on plasma TG homeostasis are inconclusive because they relied on orally administered synthetic hormone preparations or evaluated only plasma lipid concentrations but not kinetics. The purpose of this study was to evaluate the effects of systemically delivered 17β-estradiol, progesterone, and T on very low density lipoprotein-triglyceride (VLDL-TG) concentration and kinetics in postmenopausal women. VLDL-TG concentration and kinetics were evaluated by using stable isotope-labeled tracer techniques in four groups of postmenopausal women (n = 27 total) who were studied before and after treatment with either 17β-estradiol (0.1 mg/d via continuous delivery skin patch), progesterone (100 mg/d via vaginal insert) and T (12.5 mg/d via skin gel), or no intervention (control group). VLDL-TG concentration and kinetics were unchanged in the control group and not altered by T and progesterone administration. Estradiol treatment, in contrast, reduced VLDL-TG concentration by approximately 30% due to accelerated VLDL-TG plasma clearance (25.1 ± 2.5 vs. 17.4 ± 2.7 mL/min; P < .01). Estradiol, but not progesterone or T, is a major regulator of VLDL-TG metabolism.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial

PubMed Central

Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

2015-01-01

Background: The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. Objective: This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. Materials and Methods: This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. Results: The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). Conclusion: We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group. PMID:26494991

The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

PubMed

Dhondt, Marijke M M; Adriaens, Els; Roey, Jens Van; Remon, Jean Paul

2005-08-01

The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

The history of natural progesterone, the never-ending story.

PubMed

Piette, P

2018-05-28

The term progesterone should only be used for the natural hormone produced by the ovaries or included in a registered drug. The modern history of progesterone begins with the first book-length description of the female reproductive system including the corpus luteum and later with the Nobel Prize winner, Adolf Butenandt who took a crucial step when he succeeded in converting pregnanediol into a chemically pure form of progesterone, the corpus luteum hormone. The deficient production of progesterone was shown first to be the cause of the luteal-phase deficiency responsible for infertility and early pregnancy loss due to inadequate secretory transformation of the endometrium. Later, progesterone was confirmed to be the best and safest method of providing luteal-phase support in assisted reproductive technology. Progesterone provides adequate endometrial protection and is suggested to be the optimal progestagen in menopausal hormone therapy in terms of cardiovascular effects, venous thromboembolism, probably stroke and even breast cancer risk. Neuroprotective effects of progesterone have also been demonstrated in several of experimental models including cerebral ischemic stroke and Alzheimer's disease. Vaginal progesterone was shown to decrease the risk of preterm birth in women with a mid-trimester sonographic short cervix and to improve perinatal outcomes in singleton and twin gestations.

True vaginal prolapse in a bitch.

PubMed

Alan, M; Cetin, Y; Sendag, S; Eski, F

2007-08-01

Frequently, vaginal fold prolapse is the protrusion of edematous vaginal tissue into and through the opening of the vulva occurring during proestrus and estrus stages of the sexual cycle. True vaginal prolapse may occur near parturition, as the concentration of serum progesterone declines and the concentration of serum oestrogen increases. In the bitch, this type of true vaginal prolapse is a very rare condition. This short communication describes a 5-year-old female, cross-breed dog in moderate condition, weighing 33 kg, with distocia and true vaginal prolapse. Abdominal palpation and transabdominal ultrasonography revealed live and dead foetuses in the uterine horns. One dead and four live fetuses were removed from uterus by cesarean section. The ovariohysterectomy was performed after repositioning the vaginal wall with a combination of traction from within the abdomen and external manipulation through the vulva. Re-occurrence of a vaginal prolapse was not observed and the bitch recovered completely after the surgical therapy. Compared to other vaginal disorders, vaginal prolapse is an uncommon condition in the bitch. In the present case, extreme tenesmus arising from distocia may have predisposed to the vaginal prolapse. The cause of dystocia was probably the disposition of the first foetus. We concluded that the vaginal prolapse was the result of dystocia in the present case.

Clinical approach to vaginal/vestibular masses in the bitch.

PubMed

Manothaiudom, K; Johnston, S D

1991-05-01

The most common causes of vaginal/vestibular masses in the bitch are vaginal prolapse, vaginal neoplasia, and urethral neoplasia protruding into the vaginal vault. Other possible causes are clitoral enlargement, vaginal polyps, uterine prolapse, and vaginal abscessation or hematoma. Vaginal prolapse usually can be distinguished from neoplasia by the age of the patient, the time of occurrence during the estrous cycle, and the site of origin of the mass. Prolapse usually occurs in bitches under 4 years of age during proestrus, estrus, or at the end of diestrus and usually arises from the floor of the vagina, except for urethral tumors that protrude from the external urethral orifice. Appropriate diagnostic workup of bitches with vaginal vestibular masses includes complete history and physical examination, vaginal cytologic and vaginoscopic examination, retrograde vaginography or urethrocystography, serum progesterone and estradiol concentrations, and, in the case of suspect neoplasms, surgical or excision biopsy of the mass.

Does adjunctive use of progesterone in women with cerclage improve prevention of preterm birth?

PubMed

Sinkey, Rachel G; Garcia, Mercedes R; Odibo, Anthony O

2018-01-01

To evaluate outcomes among pregnancies with cerclage as compared to cerclage and adjunctive progesterone. A retrospective cohort study was performed from 1 October 2011-30 June 2015 including women with a singleton gestation with vaginal cerclage. Exclusion criteria included multiple gestations, simultaneous 17-alpha hydroxyprogesterone caproate (17-OHPC) and vaginal progesterone (vag-p) use, and patients lost to follow-up. Primary outcome was prevention of preterm birth less than 35 (PTB <35) weeks gestational age (GA). One hundred thirty-six patients met inclusion criteria; 73 women had cerclage only, 53 had cerclage and 17-OHPC, 10 had cerclage and vag-p. GA at cerclage placement was similar across groups (p = 0.068). There was a difference in prevention of PTB <35 weeks GA among groups (p = 0.035) with a trend toward earlier delivery among patients with cerclage and vag-p. Rates of PTB <35 weeks in the cerclage (29%) and cerclage and 17-OHPC groups (34%) were similar (p = 0.533). The odds ratio for risk of PTB <35 weeks among women with cerclage and vag-p as compared to all other patients was 5.21 (95%CI: 1.3-21.2). The combination of cerclage with intramuscular progesterone resulted in similar PTB prevention as compared to cerclage alone. There may be an association between cerclage, vaginal progesterone and higher rates of PTB which may be attributed to characteristics of the group rather than the therapies studied.

The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial

PubMed Central

2012-01-01

Background To assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH). Methods A prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B. Results One-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value. Conclusions The administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR. PMID:22360924

Progesterone in women with arrested premature labor, a report of a randomised clinical trial and updated meta-analysis.

PubMed

Wood, Stephen; Rabi, Yacov; Tang, Selphee; Brant, Rollin; Ross, Susan

2017-08-02

Progesterone may be effective in prevention of premature birth in some high risk populations. Women with arrested premature labor are at risk of recurrent labor and maintenance therapy with standard tocolytics has not been successful. Randomized double blinded clinical trial of daily treatment with 200 mg vaginal progesterone in women with arrested premature labor and an updated meta-analysis. The clinical trial was terminated early after 41 women were enrolled. Vaginal progesterone treatment did not change the median gestational age at delivery: 36+2 weeks versus 36+4 weeks, p = .865 nor increase the mean latency to delivery: 44.5 days versus 46.6 days, p = .841. In the updated meta-analysis, progesterone treatment did reduce delivery <37 weeks gestation and increase latency to delivery, but this treatment effect was not evident in the high quality trials: (OR 1.23, 95% CI 0.91, 1.67) and (-0.95 days, 95% CI -5.54, 3.64) respectively. Progesterone is not effective for preventing preterm birth following arrested preterm labor.

Coupled gel spreading and diffusive transport models describing microbicidal drug delivery

NASA Astrophysics Data System (ADS)

Funke, Claire; MacMillan, Kelsey; Ham, Anthony S.; Szeri, Andrew J.; Katz, David F.

2016-11-01

Gels are a drug delivery platform being evaluated for application of active pharmaceutical ingredients, termed microbicides, that act topically against infection by sexually transmitted HIV. Despite success in one Phase IIb trial of a vaginal gel delivering tenofovir, problems of user adherence to designed gel application regimen compromised results in two other trials. The microbicide field is responding to this issue by simultaneously analyzing behavioral determinants of adherence and pharmacological determinants of drug delivery. Central to both user adherence and mucosal drug delivery are gel properties (e.g. rheology) and applied volume. The specific problem to be solved here is to develop a model for how gel rheology and volume, interacting with loaded drug concentration, govern the transport of the microbicide drug tenofovir into the vaginal mucosa to its stromal layer. The analysis here builds upon our current understanding of vaginal gel deployment and drug delivery, incorporating key features of the gel's environment, fluid production and subsequent gel dilution, and vaginal wall elasticity. We consider the microbicide drug tenofovir as it is the most completely studied drug, in both in vitroand in vivostudies, for use in vaginal gel application. Our goal is to contribute to improved pharmacological understanding of gel functionality, providing a computational tool that can be used in future vaginal microbicide gel design.

Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy.

PubMed

Jain, Siddharth; Kilgore, Meredith; Edwards, Rodney K; Owen, John

2016-07-01

Preterm birth (PTB) is a significant cause of neonatal morbidity and mortality. Studies have shown that vaginal progesterone therapy for women diagnosed with shortened cervical length can reduce the risk of PTB. However, published cost-effectiveness analyses of vaginal progesterone for short cervix have not considered an appropriate range of clinically important parameters. To evaluate the cost-effectiveness of universal cervical length screening in women without a history of spontaneous PTB, assuming that all women with shortened cervical length receive progesterone to reduce the likelihood of PTB. A decision analysis model was developed to compare universal screening and no-screening strategies. The primary outcome was the cost-effectiveness ratio of both the strategies, defined as the estimated patient cost per quality-adjusted life-year (QALY) realized by the children. One-way sensitivity analyses were performed by varying progesterone efficacy to prevent PTB. A probabilistic sensitivity analysis was performed to address uncertainties in model parameter estimates. In our base-case analysis, assuming that progesterone reduces the likelihood of PTB by 11%, the incremental cost-effectiveness ratio for screening was $158,000/QALY. Sensitivity analyses show that these results are highly sensitive to the presumed efficacy of progesterone to prevent PTB. In a 1-way sensitivity analysis, screening results in cost-saving if progesterone can reduce PTB by 36%. Additionally, for screening to be cost-effective at WTP=$60,000 in three clinical scenarios, progesterone therapy has to reduce PTB by 60%, 34% and 93%. Screening is never cost-saving in the worst-case scenario or when serial ultrasounds are employed, but could be cost-saving with a two-day hospitalization only if progesterone were 64% effective. Cervical length screening and treatment with progesterone is a not a dominant, cost-effective strategy unless progesterone is more effective than has been suggested by

Rapidly disintegrating vagina retentive cream suppositories of progesterone: development, patient satisfaction and in vitro/in vivo studies.

PubMed

Bendas, Ehab Rasmy; Basalious, Emad B

2016-01-01

Our objective was to develop novel vagina retentive cream suppositories (VRCS) of progesterone having rapid disintegration and good vaginal retention. VRCS of progesterone were prepared using oil in water (o/w) emulsion of mineral oil or theobroma oil in hard fat and compared with conventional vaginal suppositories (CVS) prepared by hard fat. VRCS formulations were tested for content uniformity, disintegration, melting range, in vitro release and stability studies. The most stable formulation (VRCS I) was subjected to scaling-up manufacturing and patients' satisfaction test. The rapid disintegration, good retentive properties are applicable through the inclusion of emulsified theobroma oil rather than hydrophilic surfactant into the hard fat bases. The release profile of progesterone from VRCS I showed a biphasic pattern due to the formation of progesterone reservoir in the emulsified theobroma oil. All volunteers involved in patients' satisfaction test showed high satisfactory response to the tested formulation (VRCS). The in vivo pharmacokinetic study suggests that VRCS of progesterone provided higher rate and extent of absorption compared to hard fat based suppositories. Our results proposed that emulsified theobroma oil could be promising to solve the problems of poor patients' satisfaction and variability of drug absorption associated with hard fat suppositories.

MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

PubMed

Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2017-03-01

The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic vulvar and vaginal atrophy

PubMed Central

Constantine, Ginger D.; Simon, James A.; Pickar, James H.; Archer, David F.; Kushner, Harvey; Bernick, Brian; Gasper, Gina; Graham, Shelli; Mirkin, Sebastian

2017-01-01

Abstract Objective: To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Methods: In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4, 10, or 25 μg TX-004HR or placebo for 12 weeks. Four co-primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia. Secondary endpoints included severity of vaginal dryness and vulvar and/or vaginal itching or irritation. Endometrial histology and adverse events (AEs) were included in the safety endpoints. Results: In all, 764 women were randomized (modified intent-to-treat population, n = 747; mean age 59 y). Compared with placebo, all three doses of TX-004HR significantly improved the four co-primary endpoints (P < 0.0001 for all, except dyspareunia with 4 μg, P = 0.0149). Changes in cytology, pH, and dyspareunia were also significant at weeks 2, 6, and 8. Vaginal dryness and vaginal itching/irritation improved. Sex hormone binding globulin concentrations did not change with treatment. TX-004HR was well-tolerated, with no clinically meaningful differences in treatment-emergent AEs versus placebo, and no treatment-related serious AEs or deaths. Conclusions: TX-004HR (4, 10, and 25 μg) was safe, well-tolerated, and effective for treating moderate-to-severe dyspareunia within 2 weeks with minimal systemic estrogen exposure. This novel product may be a potential new treatment option for women experiencing postmenopausal vulvar and vaginal atrophy. PMID:27922936

Consumer preference for dinoprostone vaginal gel using stated preference discrete choice modelling.

PubMed

Taylor, Susan; Armour, Carol

2003-01-01

To assess consumer preference for two methods of induction of labour using stated preference discrete choice modelling. The methods of induction were artificial rupture of the membranes (ARM) plus oxytocin and dinoprostone (prostaglandin E(2)) vaginal gel, followed by oxytocin if necessary. Consumer preference was measured in terms of willingness to pay for each of the attributes. These attributes were the method of administration, place of care, length of time from induction to delivery, need for epidural anaesthetic, type of delivery and cost. Levels were assigned to each of the attributes. Pregnant women attending a public hospital antenatal clinic were asked to read a description of the two methods and then to choose between them in 18 different scenarios in which the levels of the attributes were varied. Women were willing to pay 11 Australian dollars for a 1% reduction in the chance of needing oxytocin as well as the gel and 55 Australian dollars for every 1 hour reduction in the length of time from induction to delivery. For a 1% reduction in the chance of needing an epidural anaesthetic or Caesarean section, women expressed a willingness to pay of 20 Australian dollars and 90 Australian dollars, respectively. All estimates were obtained in 1998 and expressed in Australian dollars (1 Australian dollar = 0.63 US dollars). Women valued the less invasive method of administration of the gel and the associated greater freedom of movement during labour. However, they valued the shorter time from induction to delivery associated with ARM plus oxytocin more highly. A policy which allows women access to the gel for up to two doses would accommodate this consumer preference.

Cellular progesterone receptor phosphorylation in response to ligands activating protein kinases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, K.V.; Peralta, W.D.; Greene, G.L.

1987-08-14

Progesterone receptors were immunoprecipitated with monoclonal antibodies KD68 from lysates of human breast carcinoma T47D cells labelled to steady state specific activity with /sup 32/Pi. The 120 kDa /sup 32/P-labelled progesterone receptor band was resolved by polyacrylamide gel electrophoresis and identified by autoradiography. Phosphoamino acid analysis revealed serine phosphorylation, but no threonine or tyrosine phosphorylation. Treatment of the /sup 32/Pi-labelled cells with EGF, TPA or dibutyryl cAMP had no significant quantitative effect on progesterone receptor phosphorylation, though the EGF receptor and the cAMP-dependent protein kinases have been reported to catalyze phosphorylation of purified avian progesterone receptor preparations in cell freemore » systems. Progesterone receptor phosphorylation on serine residues was increased by 2-fold in cells treated with 10 nM progesterone; EGF had no effect on progesterone-mediated progesterone receptor phosphorylation.« less

Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women.

PubMed

Brache, Vivian; Sitruk-Ware, Regine; Williams, Alistair; Blithe, Diana; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Tsong, Yun-Yen; Sivin, Irving; Nath, Anita; Sussman, Heather; Cochon, Leila; Miranda, Maria Jose; Reyes, Verónica; Faundes, Anibal; Mishell, Daniel

2012-05-01

Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation. This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21-40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated. Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 "4-week treatment cycles." A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%). In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women

PubMed Central

Brache, Vivian; Sitruk-Ware, Regine; Williams, Alistair; Blithe, Diana; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Tsong, Yun-Yen; Sivin, Irving; Nath, Anita; Sussman, Heather; Cochon, Leila; Miranda, Maria Jose; Reyes, Verónica; Faundes, Anibal; Mishell, Daniel

2012-01-01

Background Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600–800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation. Study Design This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21–40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated. Results Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 “4-week treatment cycles.” A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%). Conclusion In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects. PMID:22176795

The use of supersaturation for the vaginal application of microbicides: a case study with dapivirine.

PubMed

Grammen, Carolien; Plum, Jakob; Van Den Brande, Jeroen; Darville, Nicolas; Augustyns, Koen; Augustijns, Patrick; Brouwers, Joachim

2014-11-01

In this study, we investigated the potential of supersaturation for the formulation of the poorly water-soluble microbicide dapivirine (DPV) in an aqueous vaginal gel in order to enhance its vaginal tissue uptake. Different excipients such as hydroxypropylmethylcellulose, polyethylene glycol 1000, and cyclodextrins were evaluated for their ability to inhibit precipitation of supersaturated DPV in the formulation vehicle as such as well as in biorelevant media. In vitro permeation assessment across HEC-1A cell layers demonstrated an enhanced DPV flux from supersaturated gels compared with suspension gels. The best performing supersaturated gel containing 500 μM DPV (supersaturation degree of 4) in the presence of sulfobutyl ether-beta-cyclodextrin (2.5%) appeared to be stable for at least 3 months. In addition, the gel generated a significant increase in vaginal drug uptake in rabbits as compared with suspension gels. We conclude that supersaturation is a possible strategy to enhance the vaginal concentration of hydrophobic microbicides, thereby increasing permeation into the vaginal submucosa. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Designing preclinical perceptibility measures to evaluate topical vaginal gel formulations: relating user sensory perceptions and experiences to formulation properties.

PubMed

Morrow, Kathleen M; Fava, Joseph L; Rosen, Rochelle K; Vargas, Sara; Shaw, Julia G; Kojic, E Milu; Kiser, Patrick F; Friend, David R; Katz, David F

2014-01-01

Abstract The effectiveness of any biomedical prevention technology relies on both biological efficacy and behavioral adherence. Microbicide trials have been hampered by low adherence, limiting the ability to draw meaningful conclusions about product effectiveness. Central to this problem may be an inadequate conceptualization of how product properties themselves impact user experience and adherence. Our goal is to expand the current microbicide development framework to include product "perceptibility," the objective measurement of user sensory perceptions (i.e., sensations) and experiences of formulation performance during use. For vaginal gels, a set of biophysical properties, including rheological properties and measures of spreading and retention, may critically impact user experiences. Project LINK sought to characterize the user experience in this regard, and to validate measures of user sensory perceptions and experiences (USPEs) using four prototype topical vaginal gel formulations designed for pericoital use. Perceptibility scales captured a range of USPEs during the product application process (five scales), ambulation after product insertion (six scales), and during sexual activity (eight scales). Comparative statistical analyses provided empirical support for hypothesized relationships between gel properties, spreading performance, and the user experience. Project LINK provides preliminary evidence for the utility of evaluating USPEs, introducing a paradigm shift in the field of microbicide formulation design. We propose that these user sensory perceptions and experiences initiate cognitive processes in users resulting in product choice and willingness-to-use. By understanding the impact of USPEs on that process, formulation development can optimize both drug delivery and adherence.

Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

PubMed

Gök, Mehmet Koray; Özgümüş, Saadet; Demir, Kamber; Cirit, Ümüt; Pabuccuoğlu, Serhat; Cevher, Erdal; Özsoy, Yıldız; Bacınoğlu, Süleyman

2016-01-20

The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

First report of vaginal prolapse in a bitch treated with oestrogen.

PubMed

Sarrafzadeh-Rezaei, F; Saifzadeh, S; Mazaheri, R; Behfar, M

2008-06-01

Vaginal prolapse is the protrusion of edematous vaginal tissue into and through the opening of the vulva occurring during the pro-oestrus and oestrus stages of the sexual cycle. True vaginal prolapse may occur near parturition, as the concentration of serum progesterone declines and the concentration of serum oestrogen increases. In a bitch, true vaginal prolapse is a very rare condition. This case report describes an 18-month-old crossbreed bitch, weighing 40 kg presented with type III vaginal prolapse. The patient had developed vaginal prolapse after receiving oestrogen in order to oestrus induction. Subsequent to unsuccessful attempts for repositioning, ovariohysterectomy (OHE), circumferential excision of the prolapsed tissue and finally vulvoplasty were performed. There was no evidence of recurrence of the prolapse during 30 days after surgery. This case report describes type III vaginal prolapse as an unusual side effect of oestrus induction hormonal therapy in the bitch.

The role of progesterone in prevention of preterm birth

PubMed Central

Dodd, Jodie M; Crowther, Caroline A

2010-01-01

Preterm birth continues to provide an enormous challenge in the delivery of perinatal health care, and is associated with considerable short and long-term health consequences for surviving infants. Progesterone has a role in maintaining pregnancy, by suppression of the calcium–calmodulin–myosin light chain kinase system. Additionally, progesterone has recognized anti-inflammatory properties, raising a possible link between inflammatory processes, alterations in progesterone receptor expression and the onset of preterm labor. Systematic reviews of randomized controlled trials evaluating the use of intramuscular and vaginal progesterone in women considered to be at increased risk of preterm birth have been published, with primary outcomes of perinatal death, preterm birth <34 weeks, and neurodevelopmental handicap in childhood. Eleven randomized controlled trials were included in the systematic review, involving 2714 women and 3452 infants, with results presented according to the reason women were considered to be at increased risk of preterm birth. While there is a potential beneficial effect in the use of progesterone for some women considered to be at increased risk of preterm birth, primarily in the reduction in the risk of preterm birth before 34 weeks gestation, it remains unclear if the observed prolongation of pregnancy translates into improved health outcomes for the infant. PMID:21072277

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

PubMed

Jarde, A; Lutsiv, O; Park, C K; Barrett, J; Beyene, J; Saito, S; Dodd, J M; Shah, P S; Cook, J L; Biringer, A B; Giglia, L; Han, Z; Staub, K; Mundle, W; Vera, C; Sabatino, L; Liyanage, S K; McDonald, S D

2017-07-01

About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I 2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I 2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I 2  22%). In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary. © 2017 Royal College of Obstetricians and Gynaecologists.

A Pilot Study Measuring the Distribution and Permeability of a Vaginal HIV Microbicide Gel Vehicle Using Magnetic Resonance Imaging, Single Photon Emission Computed Tomography/Computed Tomography, and a Radiolabeled Small Molecule.

PubMed

Fuchs, Edward J; Schwartz, Jill L; Friend, David R; Coleman, Jenell S; Hendrix, Craig W

2015-11-01

Vaginal microbicide gels containing tenofovir have proven effective in HIV prevention, offering the advantage of reduced systemic toxicity. We studied the vaginal distribution and effect on mucosal permeability of a gel vehicle. Six premenopausal women were enrolled. In Phase 1, a spreading gel containing (99m)technetium-DTPA ((99m)Tc) radiolabel and gadolinium contrast for magnetic resonance imaging (MRI) was dosed intravaginally. MRI was obtained at 0.5, 4, and 24 h, and single photon emission computed tomography with conventional computed tomography (SPECT/CT) at 1.5, 5, and 25 h postdosing. Pads and tissues were measured for activity to determine gel loss. In Phase 2, nonoxynol-9 (N-9), containing (99m)Tc-DTPA, was dosed as a permeability control; permeability was measured in blood and urine for both phases. SPECT/CT showed the distribution of spreading gel throughout the vagina with the highest concentration of radiosignal in the fornices and ectocervix; signal intensity diminished over 25 h. MRI showed the greatest signal accumulation in the fornices, most notably 1-4 h postdosing. The median (interquartile range) isotope signal loss from the vagina through 6 h was 29.1% (15.8-39.9%). Mucosal permeability to (99m)Tc-DTPA following spreading gel was negligible, in contrast to N-9, with detectable radiosignal in plasma, peaking at 8 h (5-12). Following spreading gel dosing, 0.004% (0.001-2.04%) of the radiosignal accumulated in urine over 12 h compared to 8.31% (7.07-11.01%) with N-9, (p=0.043). Spreading gel distributed variably throughout the vagina, persisting for 24 h, with signal concentrating in the fornices and ectocervix. The spreading gel had no significant effect on vaginal mucosal permeability.

The effect of polycarbophil gel (Replens) on bacterial vaginosis: a pilot study.

PubMed

Wu, Justine P; Fielding, Stephen L; Fiscella, Kevin

2007-01-01

To determine if use of intravaginal polycarbophil gel (Replens) for 1 month will: (1) lower vaginal pH; (2) improve signs of bacterial vaginosis (BV). Seventeen women with BV self-administered polycarbophil gel every third day for 4 weeks in an open-label, prospective pilot study. Primary outcome measures included vaginal pH, presence of amines and Nugent scores. At week 4, there was improvement in Nugent scores, vaginal odor and clue cell count (p<0.05). Eleven women converted from amine positive to negative (73+/-20%). There was no significant change in vaginal pH. Polycarbophil gel is associated with improved signs of BV, although not vaginal pH.

Induction of labor using prostaglandin E2 (PGE2) vaginal gel in triacetin base. An efficacy study comparing two dosage regimens.

PubMed

Seeras, R C; Olatunbosun, O A; Pierson, R A; Turnell, R W

1995-01-01

To compare two dosage regimens for the administration of vaginal prostaglandin gel in triacetin base for induction of labor. Seventy subjects planned for elective induction of labor at term were randomized to treatment with PGE2 vaginal gel every 6 or 12 hours. The 6-hourly group received an initial dose of 1 mg, followed by 2 mg at 6 hour intervals for a maximum of two additional doses if not in active labor. The 12-hourly group had an initial dose of 2 mg followed by two additional doses at 12 hour intervals if not in active labor. Successful induction rate was higher in the 12-hourly as compared to 6-hourly gel regimen (100% vs. 91%, P > 0.05). Twelve hours after the initial dose, delivery occurred in 34% delivery had occurred in 57% and 37% respectively (P < 0.01). We found no difference in the induction-active labor interval (P > 0.05), and the induction-delivery interval (P > 0.05) between the two groups. Active labor followed a single dose of gel in 66% of the 12-hourly group compared to 40% of the 6-hourly group (P < 0.01). Syntocinon augmentation was needed in 6% of subjects in the 12-hourly group as compared to 26% in the 6-hourly group (P < 0.01). The cesarean section rate was similar in both groups. Uterine hyperstimulation occurred less frequently in the 12-hourly group (P < 0.05). The perinatal outcome was similar in both groups. The 12-hourly regimen was more effective than the 6-hourly regimen in initiating labor. The majority of the subjects in the 12 hourly group achieved labor following a single dose of gel. Induction delivery interval, however, was similar in both groups.

Designing Preclinical Perceptibility Measures to Evaluate Topical Vaginal Gel Formulations: Relating User Sensory Perceptions and Experiences to Formulation Properties

PubMed Central

Fava, Joseph L.; Rosen, Rochelle K.; Vargas, Sara; Shaw, Julia G.; Kojic, E. Milu; Kiser, Patrick F.; Friend, David R.; Katz, David F.

2014-01-01

Abstract The effectiveness of any biomedical prevention technology relies on both biological efficacy and behavioral adherence. Microbicide trials have been hampered by low adherence, limiting the ability to draw meaningful conclusions about product effectiveness. Central to this problem may be an inadequate conceptualization of how product properties themselves impact user experience and adherence. Our goal is to expand the current microbicide development framework to include product “perceptibility,” the objective measurement of user sensory perceptions (i.e., sensations) and experiences of formulation performance during use. For vaginal gels, a set of biophysical properties, including rheological properties and measures of spreading and retention, may critically impact user experiences. Project LINK sought to characterize the user experience in this regard, and to validate measures of user sensory perceptions and experiences (USPEs) using four prototype topical vaginal gel formulations designed for pericoital use. Perceptibility scales captured a range of USPEs during the product application process (five scales), ambulation after product insertion (six scales), and during sexual activity (eight scales). Comparative statistical analyses provided empirical support for hypothesized relationships between gel properties, spreading performance, and the user experience. Project LINK provides preliminary evidence for the utility of evaluating USPEs, introducing a paradigm shift in the field of microbicide formulation design. We propose that these user sensory perceptions and experiences initiate cognitive processes in users resulting in product choice and willingness-to-use. By understanding the impact of USPEs on that process, formulation development can optimize both drug delivery and adherence. PMID:24180360

Progesterone Signaling Inhibits Cervical Carcinogenesis in Mice

PubMed Central

Yoo, Young A; Son, Jieun; Mehta, Fabiola F.; DeMayo, Francesco J.; Lydon, John P.; Chung, Sang-Hyuk

2014-01-01

Human papillomavirus is the main cause of cervical cancer, yet other nonviral cofactors are also required for the disease. The uterine cervix is a hormone-responsive tissue, and female hormones have been implicated in cervical carcinogenesis. A transgenic mouse model expressing human papillomavirus oncogenes E6 and/or E7 has proven useful to study a mechanism of hormone actions in the context of this common malignancy. Estrogen and estrogen receptor α are required for the development of cervical cancer in this mouse model. Estrogen receptor α is known to up-regulate expression of the progesterone receptor, which, on activation by its ligands, either promotes or inhibits carcinogenesis, depending on the tissue context. Here, we report that progesterone receptor inhibits cervical and vaginal epithelial cell proliferation in a ligand-dependent manner. We also report that synthetic progestin medroxyprogesterone acetate promotes regression of cancers and precancerous lesions in the female lower reproductive tracts (ie, cervix and vagina) in the human papillomavirus transgenic mouse model. Our results provide the first experimental evidence that supports the hypothesis that progesterone signaling is inhibitory for cervical carcinogenesis in vivo. PMID:24012679

Successful treatment of bacterial vaginosis with a policarbophil-carbopol acidic vaginal gel: results from a randomised double-blind, placebo-controlled trial.

PubMed

Fiorilli, Angelo; Molteni, Bruno; Milani, Massimo

2005-06-01

We evaluated the efficacy of a mucoadhesive vaginal gel (MVG, Miphil) with acidic-buffering properties in bacterial vaginosis (BV). Double-blind, placebo-controlled, 12-week trial. A total of 45 non-pregnant women with BV were enrolled in the trial. Patients were treated with MVG 2.5 g or the corresponding placebo (P) daily for the first week and then every 3 days for the following 5 weeks (treatment phase) in a 2:1 ratio. All patients were followed for an additional 6 weeks without treatments (follow-up phase). Clinical cure was defined as absence of vaginal discharge, vaginal pH <4.5, a negative fish odour test and a Nugent score <7. At week 6, 28 out of 30 women (93%) in the MVG group were clinically cured in comparison with only 1 out of 15 (6%) in the P group (P=0.0001). At week 12, 86% of MVG treated women remained cured in comparison with 8% in P group (P=0.0001). At baseline, the vaginal pH was 6.1+/-0.7 in the MVG and 5.5+/-0.7 in the P group. Vaginal pH significantly (P=0.003) decreased to 4.3+/-0.3 in the MVG group. In P group non-significant modifications of vaginal pH were observed (5.1+/-0.5). Our results demonstrated that this MVG is an effective treatment of BV.

Crystallization of steroids in gels

NASA Astrophysics Data System (ADS)

Kalkura, S. Narayana; Devanarayanan, S.

1991-03-01

The crystal growth and characterization of certain steriods, viz., cholesterol, cholesteryl acetate, β-sitosterol, progesterone and testosterone, in a silica gel medium is discussed. The present study shows that the single test tube diffusion method can be used to grow crystals of steroids in a silica gel medium by the reduction of steroid solubility.

Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors.

PubMed

Dobard, Charles; Sharma, Sunita; Parikh, Urvi M; West, Rolieria; Taylor, Andrew; Martin, Amy; Pau, Chou-Pong; Hanson, Debra L; Lipscomb, Jonathan; Smith, James; Novembre, Francis; Hazuda, Daria; Garcia-Lerma, J Gerardo; Heneine, Walid

2014-03-12

Coitally delivered microbicide gels containing antiretroviral drugs are important for HIV prevention. However, to date, microbicides have contained entry or reverse transcriptase inhibitors that block early steps in virus infection and thus need to be given as a preexposure dose that interferes with sexual practices and may limit compliance. Integrase inhibitors block late steps after virus infection and therefore are more suitable for post-coital dosing. We first determined the kinetics of strand transfer in vitro and confirmed that integration begins about 6 hours after infection. We then used a repeat-challenge macaque model to assess efficacy of vaginal gels containing integrase strand transfer inhibitors when applied before or after simian/human immunodeficiency virus (SHIV) challenge. We showed that gel containing the strand transfer inhibitor L-870812 protected two of three macaques when applied 30 min before SHIV challenge. We next evaluated the efficacy of 1% raltegravir gel and demonstrated its ability to protect macaques when applied 3 hours after SHIV exposure (five of six protected; P < 0.05, Fisher's exact test). Breakthrough infections showed no evidence of drug resistance in plasma or vaginal secretions despite continued gel dosing after infection. We documented rapid vaginal absorption reflecting a short pharmacological lag time and noted that vaginal, but not plasma, virus load was substantially reduced in the breakthrough infection after raltegravir gel treatment. We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or 3 hours after virus exposure.

Mucosal integrity and inflammatory markers in the female lower genital tract as potential screening tools for vaginal microbicides.

PubMed

Su, H Irene; Schreiber, Courtney A; Fay, Courtney; Parry, Sam; Elovitz, Michal A; Zhang, Jian; Shaunik, Alka; Barnhart, Kurt

2011-11-01

In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety. A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI). Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel. Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study. Copyright © 2011 Elsevier Inc. All rights reserved.

Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis: A Dose-Ranging Study

PubMed Central

Chavoustie, Steven E.; Jacobs, Mark; Reisman, Howard A.; Waldbaum, Arthur S.; Levy, Sharon F.; Hillier, Sharon L.; Nyirjesy, Paul

2015-01-01

Objective Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration–approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. Materials and Methods This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. Results In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Conclusions Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days. PMID:24983350

Metronidazole vaginal gel 1.3% in the treatment of bacterial vaginosis: a dose-ranging study.

PubMed

Chavoustie, Steven E; Jacobs, Mark; Reisman, Howard A; Waldbaum, Arthur S; Levy, Sharon F; Hillier, Sharon L; Nyirjesy, Paul

2015-04-01

Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration-approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days.

Covert use, vaginal lubrication, and sexual pleasure: a qualitative study of urban U.S. Women in a vaginal microbicide clinical trial.

PubMed

Hoffman, Susie; Morrow, Kate M; Mantell, Joanne E; Rosen, Rochelle K; Carballo-Diéguez, Alex; Gai, Fang

2010-06-01

Using data from a U.S. clinical safety trial of tenofovir gel, a candidate microbicide, we explored the intersection of sexual pleasure and vaginal lubrication to understand whether and under what circumstances women would use a microbicide gel covertly with primary partners. This study question emerged from acceptability research in diverse settings showing that even though future microbicides are extolled as a disease prevention method that women could use without disclosing to their partners, many women assert they would inform their primary partner. Participants (N = 84), stratified by HIV-status and sexual activity (active vs. abstinent), applied the gel intra-vaginally for 14 days. At completion, quantitative acceptability data were obtained via questionnaire (N = 79) and qualitative data via small group discussions (N = 15 groups, 40 women). Quantitatively, 71% preferred a microbicide that could not be noticed by a sex partner and 86% experienced greater vaginal lubrication with daily use. Based on our analysis of the qualitative data, we suggest that women's perception that their primary partners would notice a microbicide gel is a more important reason for their caution regarding covert use than may previously have been recognized. Our findings also showed that women's assessment of the possibility of discreet, if not covert, use was strongly related to their perception of how a microbicide's added vaginal lubrication would influence their own and their partner's pleasure, as well as their partner's experience of his sexual performance. A microbicide that increases pleasure for both partners could potentially be used without engendering opposition from primary partners.

Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections: Review Article

PubMed Central

Park, Yoo Jin

2017-01-01

Bacterial vaginosis (BV) and complicated vulvovaginal candidiasis (VVC) are frequently occurring vaginal infections in postmenopausal women, caused by an imbalance in vaginal microflora. Postmenopausal women suffer from decreased ovarian hormones estrogen and progesterone. A normal, healthy vaginal microflora mainly comprises Lactobacillus species (spp.), which act beneficially as a bacterial barrier in the vagina, interfering with uropathogens. During premenopausal period, estrogen promotes vaginal colonization by lactobacilli that metabolizing glycogen and producing lactic acid, and maintains intravaginal health by lowering the intravaginal pH level. A lower vaginal pH inhibits uropathogen growth, preventing vaginal infections. Decreased estrogen secretion in postmenopausal women depletes lactobacilli and increases intravaginal pH, resulting in increased vaginal colonization by harmful microorganisms (e.g., Enterobacter, Escherichia coli, Candida, and Gardnerella). Probiotics positively effects on vaginal microflora composition by promoting the proliferation of beneficial microorganisms, alters the intravaginal microbiota composition, prevents vaginal infections in postmenopausal. Probiotics also reduce the symptoms of vaginal infections (e.g., vaginal discharge, odor, etc.), and are thus helpful for the treatment and prevention of BV and VVC. In this review article, we provide information on the intravaginal mechanism of postmenopausal vaginal infections, and describes the effectiveness of probiotics in the treatment and prevention of BV and VVC. PMID:29354612

Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections: Review Article.

PubMed

Kim, Jun-Mo; Park, Yoo Jin

2017-12-01

Bacterial vaginosis (BV) and complicated vulvovaginal candidiasis (VVC) are frequently occurring vaginal infections in postmenopausal women, caused by an imbalance in vaginal microflora. Postmenopausal women suffer from decreased ovarian hormones estrogen and progesterone. A normal, healthy vaginal microflora mainly comprises Lactobacillus species (spp.), which act beneficially as a bacterial barrier in the vagina, interfering with uropathogens. During premenopausal period, estrogen promotes vaginal colonization by lactobacilli that metabolizing glycogen and producing lactic acid, and maintains intravaginal health by lowering the intravaginal pH level. A lower vaginal pH inhibits uropathogen growth, preventing vaginal infections. Decreased estrogen secretion in postmenopausal women depletes lactobacilli and increases intravaginal pH, resulting in increased vaginal colonization by harmful microorganisms (e.g., Enterobacter , Escherichia coli , Candida , and Gardnerella ). Probiotics positively effects on vaginal microflora composition by promoting the proliferation of beneficial microorganisms, alters the intravaginal microbiota composition, prevents vaginal infections in postmenopausal. Probiotics also reduce the symptoms of vaginal infections (e.g., vaginal discharge, odor, etc.), and are thus helpful for the treatment and prevention of BV and VVC. In this review article, we provide information on the intravaginal mechanism of postmenopausal vaginal infections, and describes the effectiveness of probiotics in the treatment and prevention of BV and VVC.

Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine.

PubMed

Shukla, Vasudha; Barnhouse, Victoria; Ackerman, William E; Summerfield, Taryn L; Powell, Heather M; Leight, Jennifer L; Kniss, Douglas A; Ghadiali, Samir N

2018-01-01

The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix's extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.

Pharmacokinetic and Safety Analyses of Tenofovir and Tenofovir-Emtricitabine Vaginal Tablets in Pigtailed Macaques

PubMed Central

Pereira, Lara E.; Friend, David R.; Garber, David A.; McNicholl, Janet M.; Hendry, R. Michael; Doncel, Gustavo F.

2014-01-01

Vaginal rapidly disintegrating tablets (RDTs) containing tenofovir (TFV) or TFV and emtricitabine (FTC) were evaluated for safety and pharmacokinetics in pigtailed macaques. Two separate animal groups (n = 4) received TFV (10 mg) or TFV-FTC (10 mg each) RDTs, administered near the cervix. A third group (n = 4) received 1 ml TFV gel. Blood plasma, vaginal tissue biopsy specimens, and vaginal fluids were collected before and after product application at 0, 0.5, 1, 4, and 24 h. A disintegration time of <30 min following vaginal application of the RDTs was noted, with negligible effects on local inflammatory cytokines, vaginal pH, and microflora. TFV pharmacokinetics were generally similar for both RDTs and gel, with peak median concentrations in vaginal tissues and vaginal secretions being on the order of 104 to 105 ng/g (147 to 571 μM) and 106 ng/g (12 to 34 mM), respectively, at 1 to 4 h postdose. At 24 h, however, TFV vaginal tissue levels were more sustained after RDT dosing, with median TFV concentrations being approximately 1 log higher than those with gel dosing. FTC pharmacokinetics after combination RDT dosing were similar to those of TFV, with peak median vaginal tissue and fluid levels being on the order of 104 ng/g (374 μM) and 106 ng/g (32 mM), respectively, at 1 h postdose with levels in fluid remaining high at 24 h. RDTs are a promising alternative vaginal dosage form, delivering TFV and/or FTC at levels that would be considered inhibitory to simian-human immunodeficiency virus in the macaque vaginal microenvironment over a 24-h period. PMID:24566178

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

PubMed

Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E M; Bender Atik, Ruth; Bloemenkamp, Kitty W M; Brady, Rebecca; Briley, Annette L; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin J; Eapen, Abey; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A M; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark D; Khalaf, Yacoub; Goddijn, Mariette; Regan, Lesley; Rai, Rajendra

2015-11-26

Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

Evaluation of Progesterone Utilization and Birth Outcomes in a State Medicaid Plan.

PubMed

Hydery, Tasmina; Price, Mylissa K; Greenwood, Bonnie C; Takeshita, Mito; Kunte, Parag S; Mauro, Rose P; Lenz, Kimberly; Jeffrey, Paul L

2017-10-01

Progesterone (hydroxyprogesterone caproate injection and vaginal progesterone) has been shown to reduce preterm birth (PTB) rates by a third among pregnant women at high risk. The purpose of this analysis is to report birth outcomes and medication adherence among Massachusetts Medicaid (MassHealth) members receiving progesterone, evaluate the association between member characteristics and birth outcomes and medication adherence, and compare cost of care with a prior preterm pregnancy. This retrospective cohort study used medical claims, pharmacy claims, and prior authorization (PA) request data for MassHealth members who had a PA submitted for progesterone between January 1, 2011, and March 31, 2015. Members were excluded due to breaks in coverage, progesterone was not indicated for prevention of PTB, and if current gestational week or date of delivery was unavailable. A total of 418 members were screened for inclusion of whom 190 met criteria and 169 filled progesterone. Mean age was 29.2 years (SD = 5.23), and clinical comorbidities were identified in 90.5% of members. Consistent with clinical trials on progesterone effectiveness, 62.1% of members had a term delivery (37 wks of gestation). Among members with prior gestational age at delivery available, the average difference in gestational age between pregnancies was 8.25 weeks (SD = 6.11). In addition, 66.3% of members were adherent to progesterone based on proportion of days covered (PDC) of 0.8 or higher. The overall mean PDC was 0.79 (SD = 0.26). Despite similar birth outcomes in clinical trials and national trends, medication adherence is low in this state Medicaid program. Therefore, members may benefit from adherence support. © 2017 Pharmacotherapy Publications, Inc.

Chronic vaginal prolapse during pregnancy in a bitch.

PubMed

Memon, M A; Pavletic, M M; Kumar, M S

1993-01-15

A 4-year-old bitch was referred with chronic vaginal prolapse. It was first noticed during estrus, about 58 days prior to referral. Artificial insemination (AI) was performed twice after reducing the prolapse manually. Abdominal radiography (53 to 55 days after AI) was performed by the attending veterinarian and the bitch was determined to be not pregnant. Serum progesterone and estradiol concentrations were 1.38 ng/ml and 1.79 pg/ml, respectively. With the bitch under general anesthesia, the vaginal prolapse was partially reduced and a hysteropexy was performed. Six days after surgery, the bitch delivered a live male pup. It is recommended that bitches so affected should not be bred, and that those not required for breeding should be ovariectomized.

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women.

PubMed

Velloza, Jennifer; Heffron, Renee

2017-10-01

This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial.

PubMed

van Zijl, Maud D; Koullali, Bouchra; Naaktgeboren, Christiana A; Schuit, Ewoud; Bekedam, Dick J; Moll, Etelka; Oudijk, Martijn A; van Baal, Wilhelmina M; de Boer, Marjon A; Visser, Henricus; van Drongelen, Joris; van de Made, Flip W; Vollebregt, Karlijn C; Muller, Moira A; Bekker, Mireille N; Brons, Jozien T J; Sueters, Marieke; Langenveld, Josje; Franssen, Maureen T; Schuitemaker, Nico W; van Beek, Erik; Scheepers, Hubertina C J; de Boer, Karin; Tepe, Eveline M; Huisjes, Anjoke J M; Hooker, Angelo B; Verheijen, Evelyn C J; Papatsonis, Dimitri N; Mol, Ben Willem J; Kazemier, Brenda M; Pajkrt, Eva

2017-09-04

Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit

Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

PubMed

Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

2015-01-01

Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

Dynamics of Vaginal Bacterial Communities in Women Developing Bacterial Vaginosis, Candidiasis, or No Infection, Analyzed by PCR-Denaturing Gradient Gel Electrophoresis and Real-Time PCR▿

PubMed Central

Vitali, Beatrice; Pugliese, Ciro; Biagi, Elena; Candela, Marco; Turroni, Silvia; Bellen, Gert; Donders, Gilbert G. G.; Brigidi, Patrizia

2007-01-01

The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA. PMID:17644631

Dynamics of vaginal bacterial communities in women developing bacterial vaginosis, candidiasis, or no infection, analyzed by PCR-denaturing gradient gel electrophoresis and real-time PCR.

PubMed

Vitali, Beatrice; Pugliese, Ciro; Biagi, Elena; Candela, Marco; Turroni, Silvia; Bellen, Gert; Donders, Gilbert G G; Brigidi, Patrizia

2007-09-01

The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA.

Advanced topical drug delivery system for the management of vaginal candidiasis.

PubMed

Johal, Himmat Singh; Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

2016-01-01

Vaginal candidiasis or vulvovaginal candidiasis (VC) is a common mucosal infection of vagina, mainly caused by Candida species. The major symptoms of VC are dyspareunia, pruritis, itching, soreness, vagina as well as vulvar erythema and edema. Most common risk factors that lead to the imbalance in the vaginal micro biota are the use of antibiotics, pregnancy, diabetes mellitus, immuno suppression as in AIDS or HIV patients, frequent sexual intercourse, spermicide and intra-uterine devices and vaginal douching. Various anti-fungal drugs are available for effective treatment of VC. Different conventional vaginal formulations (creams, gels, suppositories, powder, ointment, etc.) for VC are available today but have limited efficacy because of lesser residence time on vaginal epithelium due to self-cleansing action of vagina. So to overcome this problem, an extended and intimate contact with vaginal mucosa is desired; which can be accomplished by utilizing mucoadhesive polymers. Mucoadhesive polymers have an excellent binding capacity to mucosal tissues for considerable period of time. This unique property of these polymers significantly enhances retention time of different formulations on mucosal tissues. Currently, various novel formulations such as liposomes, nano- and microparticles, micro-emulsions, bio-adhesive gel and tablets are used to control and treat VC. In this review, we focused on current status of vaginal candidiasis, conventional and nanotechnology inspired formulation approaches.

Mucoadhesive and thermogelling systems for vaginal drug delivery.

PubMed

Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

2015-09-15

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy of rifaximin vaginal tablets in treatment of bacterial vaginosis: a molecular characterization of the vaginal microbiota.

PubMed

Cruciani, Federica; Brigidi, Patrizia; Calanni, Fiorella; Lauro, Vittoria; Tacchi, Raffaella; Donders, Gilbert; Peters, Klaus; Guaschino, Secondo; Vitali, Beatrice

2012-08-01

Bacterial vaginosis (BV) is a common vaginal disorder characterized by an alteration of the vaginal bacterial morphotypes, associated with sexually transmitted infections and adverse pregnancy outcomes. The purpose of the present study was to evaluate the impact of different doses of rifaximin vaginal tablets (100 mg/day for 5 days, 25 mg/day for 5 days, and 100 mg/day for 2 days) on the vaginal microbiota of 102 European patients with BV enrolled in a multicenter, double-blind, randomized, placebo-controlled study. An integrated molecular approach based on quantitative PCR (qPCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to investigate the effects of vaginal tablets containing the antibiotic. An increase in members of the genus Lactobacillus and a decrease in the BV-related bacterial groups after the antibiotic treatment were demonstrated by qPCR. PCR-DGGE profiles confirmed the capability of rifaximin to modulate the composition of the vaginal microbial communities and to reduce their complexity. This molecular analysis supported the clinical observation that rifaximin at 25 mg/day for 5 days represents an effective treatment to be used in future pivotal studies for the treatment of BV.

Efficacy of Rifaximin Vaginal Tablets in Treatment of Bacterial Vaginosis: a Molecular Characterization of the Vaginal Microbiota

PubMed Central

Cruciani, Federica; Brigidi, Patrizia; Calanni, Fiorella; Lauro, Vittoria; Tacchi, Raffaella; Donders, Gilbert; Peters, Klaus; Guaschino, Secondo

2012-01-01

Bacterial vaginosis (BV) is a common vaginal disorder characterized by an alteration of the vaginal bacterial morphotypes, associated with sexually transmitted infections and adverse pregnancy outcomes. The purpose of the present study was to evaluate the impact of different doses of rifaximin vaginal tablets (100 mg/day for 5 days, 25 mg/day for 5 days, and 100 mg/day for 2 days) on the vaginal microbiota of 102 European patients with BV enrolled in a multicenter, double-blind, randomized, placebo-controlled study. An integrated molecular approach based on quantitative PCR (qPCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to investigate the effects of vaginal tablets containing the antibiotic. An increase in members of the genus Lactobacillus and a decrease in the BV-related bacterial groups after the antibiotic treatment were demonstrated by qPCR. PCR-DGGE profiles confirmed the capability of rifaximin to modulate the composition of the vaginal microbial communities and to reduce their complexity. This molecular analysis supported the clinical observation that rifaximin at 25 mg/day for 5 days represents an effective treatment to be used in future pivotal studies for the treatment of BV. PMID:22585228

Pre-exposure Prophylaxis adherence measured by plasma drug level in MTN-001: comparison between vaginal gel and oral tablets in two geographic regions

PubMed Central

Minnis, Alexandra M.; van der Straten, Ariane; Salee, Parichat; Hendrix, Craig W.

2016-01-01

Despite strong evidence that daily oral pre-exposure prophylaxis (PrEP) reduces HIV risk, effectiveness across studies has varied. Inconsistent adherence constitutes one explanation. Efforts to examine adherence are limited when they rely on self-reported measures. We examined recent adherence as measured by plasma tenofovir (TFV) concentration in participants of MTN-001, a phase 2 cross-over trial comparing oral tablet and vaginal gel formulations of TFV among 144 HIV-uninfected women at sites in the United States (US) and sub-Saharan Africa (SSA). Adherence to daily product use was higher in the US than in the SSA sites. Within region, however, adherence was similar between products. In the US, gel adherence was higher among married women, and lower among women using male condoms and injectable contraceptives. At the SSA sites, gel adherence was lower for younger women. Inconsistent adherence points to challenges in use of daily PrEP, even during a trial of short duration. PMID:25969178

The Vaginal Eukaryotic DNA Virome and Preterm Birth.

PubMed

Wylie, Kristine M; Wylie, Todd N; Cahill, Alison G; Macones, George A; Tuuli, Methodius G; Stout, Molly J

2018-05-05

Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Culture-independent sequencing of vaginal bacterial communities demonstrates community characteristics are associated with preterm birth, although none are specific enough to apply clinically. Viruses are important components of the vaginal microbiome and have dynamic relationships with vaginal bacterial communities. We hypothesized that vaginal eukaryotic DNA viral communities (the "vaginal virome") either alone or in the context of bacterial communities are associated with preterm birth. The objective of this study was to use high-throughput sequencing to examine the vaginal eukaryotic DNA virome in a cohort of pregnant women and examine associations between vaginal community characteristics and preterm birth. This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained at routine prenatal visits. DNA was extracted, bacterial communities were characterized by 16S rRNA gene sequencing, and eukaryotic viral communities were characterized by enrichment of viral nucleic acid with the ViroCap targeted sequence capture panel followed by nucleic acid sequencing. Viral communities were analyzed according to presence/absence of viruses, diversity, dynamics over time, and association with bacterial community data obtained from the same specimens. Sixty subjects contributed 128 vaginal swabs longitudinally across pregnancy. Twenty-four patients delivered preterm. Participants were predominantly African-American (65%). Six families of eukaryotic DNA viruses were detected in the vaginal samples. At least 1 virus was detected in 80% of women. No specific virus or group of viruses was associated with preterm delivery. Higher viral richness was significantly associated with preterm

Vaginal microbial communities from synchronized heifers and cows with reproductive disorders.

PubMed

Gonzalez Moreno, C; Fontana, C; Cocconcelli, P S; Callegari, M L; Otero, M C

2016-11-01

To evaluate changes in the resident microbial population in the cranial vaginal mucosa induced by a progesterone-releasing intravaginal device (PRID) compared to the vaginal microbiota of cows with reproductive disorders. Vaginal discharge was evaluated by clinical examination and a Vaginitis Diagnosis Score was performed by exfoliative cytology. All samples classified as positive and some classified as negative by clinical evaluation were later diagnosed as positive for vaginitis by cytological analysis. Bacterial diversity profiles were performed by PCR-DGGE and clustered according to the reproductive health status of the specimens, revealing a correspondence between the structures of the communities in the vagina and the clinical profile. Representative bands from each group were sequenced and identified as Ruminococcus sp., Dialister sp., Escherichia sp./Shigella sp., Virgibacillus sp., Campylobacter sp., Helcoccoccus sp., Staphylococcus sp., Bacillus sp., Actinopolymorpha sp., Exiguobacterium sp., Haemophilus sp./Histophilus sp., Aeribacillus sp., Porphyromonas sp., Lactobacillus sp. and Clostridium sp. Our results contribute to the knowledge of the vaginal microbiome in synchronized heifers showing positive or negative clinical vaginitis. This study contributes to the understanding of a dynamic vaginal colonization by bacterial consortiums during the synchronization with a widely used PRID protocol. Also, the results reveal the presence of well-known metritis-related pathogens as well as emerging uterine opportunistic pathogens. The provided information will allow to carry out further studies to elucidate functional roles of these native micro-organisms in the bovine reproductive tract. © 2016 The Society for Applied Microbiology.

A Phase 1 Trial to Assess the Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics of a Novel Dapivirine Vaginal Film.

PubMed

Bunge, Katherine E; Dezzutti, Charlene S; Rohan, Lisa C; Hendrix, Craig W; Marzinke, Mark A; Richardson-Harman, Nicola; Moncla, Bernard J; Devlin, Brid; Meyn, Leslie A; Spiegel, Hans M L; Hillier, Sharon L

2016-04-15

Films may deliver antiretroviral drugs efficiently to mucosal tissues. In this first in-human trial of a vaginal film for delivering the nonnucleoside reverse transcriptase inhibitor dapivirine, safety, pharmacokinetics, and pharmacodynamics of film and gel formulations were compared with placebo. Sixty-one healthy HIV-negative women were randomized to daily dapivirine (0.05%) or placebo gel, or dapivirine (1.25 mg) or placebo film for seven days. The proportion of participants experiencing grade 2 and higher adverse events related to study product were compared. Plasma dapivirine concentrations were quantified. Paired cervical and vaginal tissue biopsies obtained ∼2 hours after the last dose were measured for tissue drug concentration and exposed to HIV in an ex vivo challenge assay. Two grade 2 related adverse events occurred in the placebo film group. Women randomized to gel and film products had 4 log10 higher of dapivirine in cervical and vaginal tissues than plasma. Although gel and film users had comparable plasma dapivirine concentrations, tissue concentrations of dapivirine were 3-5 times higher in the gel users when compared with film users. HIV replication in the ex vivo challenge assay was significantly reduced in vaginal tissues from women randomized to dapivirine film or gel; furthermore, tissue drug concentrations were highly correlated with HIV protection. Women rated the film more comfortable with less leakage but found it more difficult to insert than gel. Both film and gel delivered dapivirine at concentrations sufficient to block HIV ex vivo. This proof-of-concept study suggests film formulations for microbicides merit further investigation.

A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of a novel dapivirine vaginal film

PubMed Central

Bunge, Authors: Katherine E.; Dezzutti, Charlene S.; Rohan, Lisa C.; Hendrix, Craig W.; Marzinke, Mark A.; Richardson-Harman, Nicola; Moncla, Bernard J.; Devlin, Brid; Meyn, Leslie A.; M.L.Spiegel, Hans; Hillier, Sharon L.

2016-01-01

Background Films may deliver antiretroviral drugs efficiently to mucosal tissues. In this first in-human trial of a vaginal film for delivering the non-nucleoside reverse transcriptase inhibitor dapivirine, safety, pharmacokinetics, and pharmacodynamics of film and gel formulations were compared to placebo. Methods 61 healthy HIV negative women were randomized to daily dapivirine (0.05%) or placebo gel, or dapivirine (1.25mg) or placebo film for seven days. The proportion of participants experiencing Grade 2 and higher adverse events related to study product were compared. Plasma dapivirine concentrations were quantified. Paired cervical and vaginal tissue biopsies obtained ∼2 hours following the last dose were measured for tissue drug concentration and exposed to HIV in an ex vivo challenge assay. Results Two Grade 2 related AEs occurred in the placebo film group. Women randomized to gel and film products had 4 log10 higher of dapivirine in cervical and vaginal tissues than plasma. While gel and film users had comparable plasma dapivirine concentrations, tissue concentrations of dapivirine were 3 to 5 times higher in the gel users when compared to film users. HIV replication in the ex vivo challenge assay was significantly reduced in vaginal tissues from women randomized to dapivirine film or gel; furthermore, tissue drug concentrations were highly correlated with HIV protection. Women rated the film more comfortable with less leakage, but found it more difficult to insert than gel. Discussion Both film and gel delivered dapivirine at concentrations sufficient to block HIV ex vivo. This proof of concept study suggests film formulations for microbicides merit further investigation. PMID:26565716

Neonatal Progesterone Programs Adult Uterine Responses to Progesterone and Susceptibility to Uterine Dysfunction

PubMed Central

Rumi, M. A. Karim; Kubota, Kaiyu; Chakraborty, Damayanti; Chien, Jeremy; Roby, Katherine F.

2015-01-01

In this report, we investigated the consequences of neonatal progesterone exposure on adult rat uterine function. Female pups were subcutaneously injected with vehicle or progesterone from postnatal days 3 to 9. Early progesterone exposure affected endometrial gland biogenesis, puberty, decidualization, and fertility. Because decidualization and pregnancy success are directly linked to progesterone action on the uterus, we investigated the responsiveness of the adult uterus to progesterone. We first identified progesterone-dependent uterine gene expression using RNA sequencing and quantitative RT-PCR in Holtzman Sprague-Dawley rats and progesterone-resistant Brown Norway rats. The impact of neonatal progesterone treatment on adult uterine progesterone responsiveness was next investigated using quantitative RT-PCR. Progesterone resistance affected the spectrum and total number of progesterone-responsive genes and the magnitude of uterine responses for a subset of progesterone targets. Several progesterone-responsive genes in adult uterus exhibited significantly dampened responses in neonatally progesterone-treated females compared with those of vehicle-treated controls, whereas other progesterone-responsive transcripts did not differ between female rats exposed to vehicle or progesterone as neonates. The organizational actions of progesterone on the uterus were dependent on signaling through the progesterone receptor but not estrogen receptor 1. To summarize, neonatal progesterone exposure leads to disturbances in endometrial gland biogenesis, progesterone resistance, and uterine dysfunction. Neonatal progesterone effectively programs adult uterine responsiveness to progesterone. PMID:26204463

Comparison of the vaginal environment of Macaca mulatta and Macaca nemestrina throughout the menstrual cycle

PubMed Central

Hadzic, Sarah V.; Wang, Xiaolei; Dufour, Jason; Doyle, Lara; Marx, Preston A.; Lackner, Andrew A.; Paulsen, Daniel B.; Veazey, Ronald S.

2014-01-01

Problem Pigtail macaques, Macaca nemestrina (PT) are more susceptible to vaginal transmission of simian immunodeficiency virus (SIV) and other sexually transmitted diseases (STD) than rhesus macaques (RM). However, comparative studies to explore the reasons for these differences are lacking. Method of Study Here we compared differences in hormone levels and vaginal mucosal anatomy and thickness of RM and PT through different stages of the menstrual cycle. Concentrations of plasma estradiol (E2) and progesterone (P4) were determined weekly, and vaginal biopsies examined at day 0 and 14 of the menstrual cycle. Results Consistent changes in vaginal epithelial thickness occurred at different stages of the menstrual cycle. In both species, the vaginal epithelium was significantly thicker in the follicular than in luteal phase. Keratinized epithelium was strikingly much more prominent in RM, especially during the luteal phase. Further, the vaginal epithelium was significantly thinner and the P4:E2 ratio was higher in PT during luteal phase than RM. Conclusions Striking anatomical differences in the vaginal epithelium between rhesus and pigtail macaques combined with differences in P4:E2 ratio support the hypothesis that thinning and less keratinization of the vaginal epithelium may be involved in the greater susceptibility of pigtail macaques to vaginal transmission of SIV or other STD. PMID:24521395

Atrophic Vaginitis in Breast Cancer Survivors: A Difficult Survivorship Issue

PubMed Central

Lester, Joanne; Pahouja, Gaurav; Andersen, Barbara; Lustberg, Maryam

2015-01-01

Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors. PMID:25815692

Atrophic vaginitis in breast cancer survivors: a difficult survivorship issue.

PubMed

Lester, Joanne; Pahouja, Gaurav; Andersen, Barbara; Lustberg, Maryam

2015-03-25

Management of breast cancer includes systematic therapies including chemotherapy and endocrine therapy can lead to a variety of symptoms that can impair the quality of life of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of circulating estrogen to urinary and vaginal receptors, is commonly experienced by this group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness, dyspareunia, and irritation of genital skin, pruritus, burning, vaginal discharge, and soreness. The diagnosis of atrophic vaginitis is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Lifestyle modifications can be helpful but are usually insufficient to significantly improve symptoms. Non-hormonal vaginal therapies may provide additional relief by increasing vaginal moisture and fluid. Systemic estrogen therapy is contraindicated in breast cancer survivors. Continued investigations of various treatments for atrophic vaginitis are necessary. Local estrogen-based therapies, DHEA, testosterone, and pH-balanced gels continue to be evaluated in ongoing studies. Definitive results are needed pertaining to the safety of topical estrogens in breast cancer survivors.

The influence of social constructs of hegemonic masculinity and sexual behaviour on acceptability of vaginal microbicides in Zambia.

PubMed

Mweemba, Oliver; Dixey, Rachael; Bond, Virginia; White, Alan

2018-07-01

Vaginal microbicides are heralded as a woman's HIV prevention method. This study, conducted in a microbicide clinical trial setting in Zambia, explored how the social construction of masculinity and sexual behaviour influenced the acceptability of vaginal microbicides. The data were generated from 18 In-depth Interviews and 8 Focus Group Discussions. The data were analysed thematically. The study found that hegemonic masculinity influenced the use of vaginal microbicides positively and negatively, in multiple ways including: decision to initiate gel use, autonomous use of the gel, and consistent use of the gel. Men were seen as heads of households and decision-makers who approved their partners' intentions to initiate gel use. Autonomous gel use by women was not supported because it challenged men's dominant position in sexual matters and at a family level. The socially accepted notion that men engaged in multiple sexual relationships also influenced women's decision to use the gel. Sustained gel use depended on the perceived effect of the gel on men's sexual desires, sexual performance, fertility, and sexual behaviour. This study suggests that acceptability of microbicides partially lies within the realm of men, with use constrained and dictated by cultural constructs and practice of masculinity and gender.

A Temperature-Monitoring Vaginal Ring for Measuring Adherence

PubMed Central

Boyd, Peter; Desjardins, Delphine; Kumar, Sandeep; Fetherston, Susan M.; Le-Grand, Roger; Dereuddre-Bosquet, Nathalie; Helgadóttir, Berglind; Bjarnason, Ásgeir; Narasimhan, Manjula; Malcolm, R. Karl

2015-01-01

Background Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established. Methods A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal. Results In vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques. Conclusions Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials. PMID:25965956

A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis.

PubMed

Schwebke, Jane R; Marrazzo, Jeanne; Beelen, Andrew P; Sobel, Jack D

2015-07-01

Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative "whiff test," and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV.

In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida spp. and Probiotic Vaginal Microbiota.

PubMed

Di Vito, Maura; Mattarelli, Paola; Modesto, Monica; Girolamo, Antonietta; Ballardini, Milva; Tamburro, Annunziata; Meledandri, Marcello; Mondello, Francesca

2015-10-01

The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO-VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R-215 and Lactobacillus acidophilus R-52) was tested. Both TTO-VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo-VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations < 2% v/v, they remained viable. TTO-VS exhibits, in vitro, a selective fungicidal action, slightly affecting only the Bifidobacteriun animalis strain growth belonging to the vaginal microbiota. In vivo studies are needed to confirm the efficacy to prevent acute or recurrent vaginal candidiasis. Copyright © 2015 John Wiley & Sons, Ltd.

Glycerol Monolaurate Does Not Alter Rhesus Macaque (Macaca mulatta) Vaginal Lactobacilli and Is Safe for Chronic Use▿

PubMed Central

Schlievert, Patrick M.; Strandberg, Kristi L.; Brosnahan, Amanda J.; Peterson, Marnie L.; Pambuccian, Stefan E.; Nephew, Karla R.; Brunner, Kevin G.; Schultz-Darken, Nancy J.; Haase, Ashley T.

2008-01-01

Glycerol monolaurate (GML) is a fatty acid monoester that inhibits growth and exotoxin production of vaginal pathogens and cytokine production by vaginal epithelial cells. Because of these activities, and because of the importance of cytokine-mediated immune activation in human immunodeficiency virus type 1 (HIV-1) transmission to women, our laboratories are performing studies on the potential efficacy of GML as a topical microbicide to interfere with HIV-1 transmission in the simian immunodeficiency virus-rhesus macaque model. While GML is generally recognized as safe by the FDA for topical use, its safety for chronic use and effects on normal vaginal microflora in this animal model have not been evaluated. GML was therefore tested both in vitro for its effects on vaginal flora lactobacilli and in vivo as a 5% gel administered vaginally to monkeys. In vitro studies demonstrated that lactobacilli are not killed by GML; GML blocks the loss of their viability in stationary phase and does not interfere with lactic acid production. GML (5% gel) does not quantitatively alter monkey aerobic vaginal microflora compared to vehicle control gel. Lactobacilli and coagulase-negative staphylococci are the dominant vaginal aerobic microflora, with beta-hemolytic streptococci, Staphylococcus aureus, and yeasts sporadically present; gram-negative rods are not part of their vaginal flora. Colposcopy and biopsy studies indicate that GML does not alter normal mucosal integrity and does not induce inflammation; instead, GML reduces epithelial cell production of interleukin 8. The studies suggest that GML is safe for chronic use in monkeys when applied vaginally; it does not alter either mucosal microflora or integrity. PMID:18838587

Plasma progesterone levels and cocaine-seeking in freely cycling female rats across the estrous cycle

PubMed Central

Feltenstein, Matthew W.; See, Ronald E.

2007-01-01

Previous studies have reported sex and estrous cycle dependent differences in the reinstatement of cocaine-seeking triggered by cocaine injections or drug-paired cues. However, the relationship between estradiol or progesterone levels and cocaine-seeking in a reinstatement model of relapse has not been explored. Thus, we examined changes in plasma hormone levels during cocaine-taking and cocaine-seeking behaviors in gonadally intact female rats. Rats self-administered cocaine (0.5 mg/kg/infusion) during daily 2-h sessions, followed by extinction. For reinstatement, cocaine (0, 5, or 10 mg/kg, i.p.) was administered 30 min prior to testing. Vaginal smears and blood samples were collected prior to and during chronic cocaine self-administration, extinction, and reinstatement testing. Relative to nonestrous females, females in estrus showed greater responding during self-administration, extinction, and during cocaine-primed reinstatement. The highest progesterone levels were noted at the time of lowest cocaine-seeking (proestrus) and the lowest levels of progesterone occurred at the time of highest cocaine-seeking (estrus). In contrast, plasma estradiol levels did not show any clear pattern with cocaine-seeking. These data from an animal model of relapse supports recent clinical evidence that progesterone reduces subjective craving in cocaine-dependent women. Overall, these results suggest that progesterone administration may be a useful intervention for reducing the incidence of relapse. PMID:17240083

Plasma progesterone levels and cocaine-seeking in freely cycling female rats across the estrous cycle.

PubMed

Feltenstein, Matthew W; See, Ronald E

2007-07-10

Previous studies have reported sex and estrous cycle-dependent differences in the reinstatement of cocaine-seeking triggered by cocaine injections or drug-paired cues. However, the relationship between estradiol or progesterone levels and cocaine-seeking in a reinstatement model of relapse has not been explored. Thus, we examined changes in plasma hormone levels during cocaine-taking and -seeking behaviors in gonadally intact female rats. Rats self-administered cocaine (0.5mg/kg infusion) during daily 2-h sessions, followed by extinction. For reinstatement, cocaine (0, 5, or 10mg/kg, i.p.) was administered 30 min prior to testing. Vaginal smears and blood samples were collected prior to and during chronic cocaine self-administration, extinction, and reinstatement testing. Relative to non-estrous females, females in estrus showed greater responding during self-administration, extinction, and during cocaine-primed reinstatement. The highest progesterone levels were noted at the time of lowest cocaine-seeking (proestrus) and the lowest levels of progesterone occurred at the time of highest cocaine-seeking (estrus). In contrast, plasma estradiol levels did not show any clear pattern with cocaine-seeking. These data from an animal model of relapse supports recent clinical evidence that progesterone reduces subjective craving in cocaine-dependent women. Overall, these results suggest that progesterone administration may be a useful intervention for reducing the incidence of relapse.

Acceptability of Carraguard, a candidate microbicide and methyl cellulose placebo vaginal gels among HIV-positive women and men in Durban, South Africa

PubMed Central

Ramjee, Gita; Morar, Neetha S; Braunstein, Sarah; Friedland, Barbara; Jones, Heidi; van de Wijgert, Janneke

2007-01-01

Background and Methods When on the market, microbicides are likely to be used by individuals who do not know their HIV status. Hence, assessment of safety and acceptability among HIV positive men and women is important. Acceptability of Carraguard, the Population Council's lead microbicide candidate was assessed in a Phase I safety study among healthy HIV-positive sexually abstinent women and men, and sexually active women (20 per group), in Durban, South Africa. Participants were randomized to use Carraguard gel, placebo gel, or no product. All women in the gel arms applied 4 ml gel vaginally every evening for 14 intermenstrual days (women in the sexually active group inserted gel within 1 hour prior to sex on days when sex occurred), and sexually abstinent men applied gel directly to the penis every evening for 7 days. Acceptability was assessed by face-to-face structured questionnaires and semi-structured in-depth interviews with all participants. Gel use questions were applicable to participants in the gel arms only (13 sexually abstinent women, 14 sexually active women, and 13 abstinent men). Results Overall, 93% of the women liked the study gel (Carraguard or placebo) very much, 4% disliked it somewhat, and 4% were neutral. 15% of men and women disliked the gel's color, smell, or packaging. Most women and men reported never experiencing pain or irritation during or after gel application. Although over two thirds of the women preferred some lubrication during sex, some of the women felt that the gel was frequently too wet. Twenty-one percent of women and 42% of men said they felt covert use of a microbicide would be acceptable. Over 60% of women and men would prefer to use a microbicide alone instead of using it with a condom. Conclusion Acceptability of Carraguard among HIV-positive women and men in Durban was good. The wetness experienced by the women may be attributed to the delivery of gel volume. The applicator was designed to deliver 4 mls whereas in

Comparison of the vaginal environment of Macaca mulatta and Macaca nemestrina throughout the menstrual cycle.

PubMed

Hadzic, Sarah V; Wang, Xiaolei; Dufour, Jason; Doyle, Lara; Marx, Preston A; Lackner, Andrew A; Paulsen, Daniel B; Veazey, Ronald S

2014-04-01

Pigtail macaques, Macaca nemestrina (PT), are more susceptible to vaginal transmission of simian immunodeficiency virus (SIV) and other sexually transmitted diseases (STD) than rhesus macaques (RM). However, comparative studies to explore the reasons for these differences are lacking. Here, we compared differences in hormone levels and vaginal mucosal anatomy and thickness of RM and PT through different stages of the menstrual cycle. Concentrations of plasma estradiol (E2) and progesterone (P4) were determined weekly, and vaginal biopsies examined at days 0 and 14 of the menstrual cycle. Consistent changes in vaginal epithelial thickness occurred at different stages of the menstrual cycle. In both species, the vaginal epithelium was significantly thicker in the follicular than in luteal phase. Keratinized epithelium was strikingly much more prominent in RM, especially during the luteal phase. Further, the vaginal epithelium was significantly thinner, and the P4:E2 ratio was higher in PT during luteal phase than RM. Striking anatomic differences in the vaginal epithelium between rhesus and pigtail macaques combined with differences in P4:E2 ratio support the hypothesis that thinning and less keratinization of the vaginal epithelium may be involved in the greater susceptibility of pigtail macaques to vaginal transmission of SIV or other STD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss.

PubMed

Stephenson, Mary D; McQueen, Dana; Winter, Michelle; Kliman, Harvey J

2017-03-01

To assess the effectiveness of luteal start vaginal micronized P in a recurrent pregnancy loss (RPL) cohort. Observational cohort study using prospectively collected data. Not applicable. Women seen between 2004 and 2012 with a history of two or more unexplained pregnancy losses <10 weeks in size; endometrial biopsy (EB) performed 9-11 days after LH surge; and one or more subsequent pregnancy(ies). Women were excluded if concomitant findings, such as endometritis, maturation delay, or glandular-stromal dyssynchrony, were identified on EB. Vaginal micronized P was prescribed at a dose of 100-200 mg every 12 hours starting 3 days after LH surge (luteal start) if glandular epithelial nuclear cyclin E (nCyclinE) expression was elevated (>20%) in endometrial glands or empirically despite normal nCyclinE (≤20%). Women with normal nCyclinE (≤20%) who did not receive P were used as controls. Pregnancy success was an ongoing pregnancy >10 weeks in size. One hundred sixteen women met the inclusion criteria, of whom 51% (n = 59) had elevated nCyclinE and 49% (n = 57) had normal nCyclinE. Pregnancy success in the 59 women with elevated nCyclinE significantly improved after intervention: 6% (16/255) in prior pregnancies versus 69% (57/83) in subsequent pregnancies. Pregnancy success in subsequent pregnancies was higher in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio = 2.1 (95% confidence interval, 1.0-4.4). In this study, we found that the use of luteal start vaginal micronized P was associated with improved pregnancy success in a strictly defined cohort of women with RPL. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel

PubMed Central

Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.

2011-01-01

Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430

A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

PubMed Central

Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

2015-01-01

Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

Adrenocortical nuclear progesterone-binding protein: Identification by photoaffinity labeling and evidence for deoxyribonucleic acid binding and stimulation by adrenocorticotropin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demura, T.; Driscoll, W.J.; Lee, Y.C.

1991-01-01

Nuclei of the guinea pig adrenal cortex contain a protein that specifically binds progesterone and that, biochemically, is clearly distinct from the classical progesterone receptor. The adrenocortical nuclear progesterone-binding protein has now been purified more than 2000-fold by steroid-affinity chromatography with a 75% yield. The purified protein preparation demonstrated three major bands on sodium dodecyl sulfate-polyacrylamide gel of 79K, 74K, and 50K. To determine which of the three might represent the progesterone-binding protein, steroid photoaffinity labeling was performed which resulted in the specific and exclusive labeling of a 50K band. Thus, the adrenocortical nuclear progesterone-binding protein appears to be distinctmore » from the classical progesterone receptor not only biochemically, but also on the basis of molecular size. To test whether the adrenocortical nuclear progesterone-binding protein can be hormonally stimulated, guinea pigs were treated with ACTH. The chronic administration of ACTH caused a 4- to 6-fold increase in the specific progesterone binding capacity without a change in the binding affinity. There appeared to be no significant difference in nuclear progesterone binding between the zona fasciculata and zona reticularis. This finding suggests a mediating role for the progesterone-binding protein in ACTH action. In addition, the nuclear progesterone-binding protein bound to nonspecific DNA sequences, further suggesting a possible transcriptional regulatory role.« less

Trial protocol OPPTIMUM– Does progesterone prophylaxis for the prevention of preterm labour improve outcome?

PubMed Central

2012-01-01

Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome. Trial registration ISRCTN14568373 PMID

Characterisation of protein stability in rod-insert vaginal rings.

PubMed

Pattani, Aditya; Lowry, Deborah; Curran, Rhonda M; McGrath, Stephanie; Kett, Vicky L; Andrews, Gavin P; Malcolm, R Karl

2012-07-01

A major goal in vaccine development is elimination of the 'cold chain', the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDI-TOF and qualitative precipitate solubility measurements. When stored at 4 °C, but not when stored at 40 °C/75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 °C/75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation compared to the original formulation when stored at 40 °C/75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general. Copyright

Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.

PubMed

Kelly, Anthony J; Malik, Sidra; Smith, Lee; Kavanagh, Josephine; Thomas, Jane

2009-10-07

Prostaglandins have been used for induction of labour since the 1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was considered unsuitable for a number of reasons. With the development of alternative routes of administration, comparisons were made between various formulations of vaginal prostaglandins. To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009) and bibliographies of relevant papers. Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. We assessed studies and extracted data independently. Sixty-three (10,441 women) have been included.Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18.1% versus 98.9%, risk ratio (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, two trials, 384 women). The risk of the cervix remaining unfavourable or unchanged was reduced (21.6% versus 40.3%, RR 0.46, 95% CI 0.35 to 0.62, five trials, 467 women); and the risk of oxytocin augmentation reduced (35.1% versus 43.8%, RR 0.83, 95% CI 0.73 to 0.94, 12 trials, 1321 women) when PGE2 was compared to placebo. There was no evidence of a difference between caesarean section rates, although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.4% versus 0.49%, RR 4.14, 95% CI 1.93 to 8.90, 14 trials, 1259 women).PGE2 tablet, gel and pessary appear to be as efficacious as each other and the use of sustained release PGE2 inserts appear to be associated with a reduction in instrumental vaginal delivery rates (9.9 % versus 19.5%, RR 0

Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

PubMed

Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

2017-03-27

Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P < 0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (P = 0.07). Plasma TFV and TFV diphosphate concentrations in tissues and vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

Progesterone-dependent sexual behavior and protein patterns in the ventromedial hypothalamus of the adult female rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montemayor, M.E.; Roy, E.J.; Giometti, C.S.

1994-09-01

Controversy exists concerning mechanisms by which progesterone exerts central nervous system effects on behavior. Progesterone may affect behavior by genomic regulation of protein synthesis. Alternatively, it may work through non-genomic mechanisms, consistent with its short latency to act. Recent work suggests that progesterone may elicit its effects on sexual behavior by more than one mechanism in a tissue specific manner. In the present study, we have examined whether progesterone facilitation of sexual behavior is correlated with modification of protein synthesis patterns in the ventromedial hypothalamus (VMH). Ovariectomized rats were divided into three groups: estradiol (4 ug/ka at 0 and 18more » hrs), estradiol (at 0 and 18 hrs) plus progesterone (2 mg/kg at 37 hrs), and vehicle only. {sup 35}S-labeled cysteine and methionine were bilaterally infused into the VMH at 37 hrs (the time of progesterone administration). Following 4 hrs of infusion, animals were tested for sexual behavior and sacrificed. Newly synthesized VMH proteins were separated by two dimensional gel electrophoresis followed by fluorography. Analysis of approximately 660 spots/fluorogram in two independent replications indicated that no protein was completely induced or lost as a result of being treated with progesterone. The abundances of several proteins were significantly altered in response to progesterone treatment in each replication; however, none were changed in abundance in both replications. These findings present no evidence that progesterone causes detectable alterations in VIMH protein patterns between 10-100 kDa in the 4.8-6.7 apparent pI range.« less

Mucus-Penetrating Nanoparticles for Vaginal Drug Delivery Protect Against Herpes Simplex Virus

PubMed Central

Ensign, Laura M.; Tang, Benjamin C.; Wang, Ying-Ying; Tse, Terence A.; Hoen, Timothy; Cone, Richard; Hanes, Justin

2013-01-01

Incomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We investigated vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution. Moreover, when delivered hypotonically, MPPs were transported advectively (versus diffusively) through mucus deep into vaginal folds (rugae) within minutes. By penetrating into the deepest mucus layers, more MPPs were retained in the vaginal tract after 6 h compared to CPs. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then developed MPPs composed of acyclovir monophosphate (ACVp). When administered prior to vaginal herpes simplex virus 2 (HSV-2) challenge, ACVp-MPPs protected 53% of mice, compared to only 16% protected by soluble drug. Overall, MPPs improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week. PMID:22700955

Progesterone and Neuroprotection

PubMed Central

Singh, Meharvan; Su, Chang

2012-01-01

Summary Numerous studies aimed at identifying the role of estrogen on the brain have used the ovariectomized rodent as the experimental model. And while estrogen intervention in these animals have, at least partially, restored cholinergic, neurotrophin and cognitive deficits seen in the ovariectomized animal, it is worth considering that the removal of the ovaries results in the loss of not only circulating estrogen but of circulating progesterone as well. As such, the various deficits associated with ovariectomy may be attributed to the loss of progesterone as well. Similarly, one must also consider the fact that the human menopause results in the precipitous decline of not just circulating estrogens, but in circulating progesterone as well and as such, the increased risk for diseases such as Alzheimer’s disease during the postmenopausal period could also be contributed by this loss of progesterone. In fact, progesterone has been shown to exert neuroprotective effects, both in cell models, animal models and in humans. Here, we review the evidence that supports the neuroprotective effects of progesterone and discuss the various mechanisms that are thought to mediate these protective effects. We also discuss the receptor pharmacology of progesterone’s neuroprotective effects and present a conceptual model of progesterone action that supports the complementary effects of membrane-associated and classical intracellular progesterone receptors. In addition, we discuss fundamental differences in the neurobiology of progesterone and the clinically used, synthetic progestin, medroxyprogesterone acetate that may offer an explanation for the negative findings of the combined estrogen/progestin arm of the Women’s Health Initiative-Memory Study (WHIMS) and suggest that the type of progestin used may dictate the outcome of either pre-clinical or clinical studies that addresses brain function. PMID:22732134

Noncomparative contraceptive efficacy of cellulose sulfate gel.

PubMed

Mauck, Christine K; Freziers, Ron G; Walsh, Terri L; Peacock, Karen; Schwartz, Jill L; Callahan, Marianne M

2008-03-01

To estimate the 6-month cumulative probability of pregnancy, short-term adverse effects, and acceptability of cellulose sulfate vaginal contraceptive gel. Two hundred fertile heterosexual couples were enrolled in this single-center, phase II, 6-month noncomparative study conducted at the California Family Health Council in Los Angeles, California. Couples did not desire pregnancy, were at low risk for sexually transmitted diseases, and agreed to use 3.5 mL of cellulose sulfate gel intravaginally before each coital act as their primary means of contraception. Scheduled follow-up visits took place after one menstrual cycle and at study completion, which occurred after 6 months and six menstrual cycles had elapsed. In addition, participants were instructed to call the site at the onset of each menses to review their diary cards. The cumulative probabilities of pregnancy during 6 months and six cycles of typical use were 13.4% (95% confidence interval [CI] 7.5-19.4%) and 13.9% (95% CI 7.7-20.2%), respectively, and during 6 cycles of correct and consistent ("perfect") use: 3.9% (95% CI 0.0-9.2%). Slightly over one fourth of the women and one man reported experiencing gel-related adverse events, two thirds of which were mild and only possibly related to the gel. Three quarters of women and men reported that they would buy cellulose sulfate gel for contraception. Cellulose sulfate vaginal gel yields pregnancy rates comparable to nonoxynol-9 and few adverse events among couples at low risk for sexually transmitted diseases.

Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery.

PubMed

Petricevic, Ljubomir; Domig, Konrad J; Nierscher, Franz Josef; Sandhofer, Michael J; Fidesser, Maria; Krondorfer, Iris; Husslein, Peter; Kneifel, Wolfgang; Kiss, Herbert

2014-05-30

The presence of an abnormal vaginal microflora in early pregnancy is a risk factor for preterm delivery. There is no investigation on vaginal flora dominated by lactic acid bacteria and possible association with preterm delivery. We assessed the dominant vaginal Lactobacillus species in healthy pregnant women in early pregnancy in relation to pregnancy outcome. We observed 111 low risk pregnant women with a normal vaginal microflora 11 + 0 to 14 + 0 weeks of pregnancy without subjective complaints. Vaginal smears were taken for the identification of lactobacilli using denaturing gradient gel electrophoresis (DGGE). Pregnancy outcome was recorded as term or preterm delivery (limit 36 + 6 weeks of gestation). The diversity of Lactobacillus species in term vs. preterm was the main outcome measure. L. iners alone was detected in 11 from 13 (85%) women who delivered preterm. By contrast, L. iners alone was detected in only 16 from 98 (16%) women who delivered at term (p < 0.001). Fifty six percent women that delivered at term and 8% women that delivered preterm had two or more vaginal Lactobacillus spp. at the same time. This study suggests that dominating L. iners alone detected in vaginal smears of healthy women in early pregnancy might be associated with preterm delivery.

Coating flow of an anti-HIV microbicide gel: boundary dilution and yield stress

NASA Astrophysics Data System (ADS)

Szeri, Andrew J.; Tasoglu, Savas; Park, Su Chan; Katz, David F.

2010-11-01

A recent study has confirmed, for the first time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, significantly inhibits sexual HIV transmission to women [1]. However, the gel for this drug, and anti-HIV microbicide gels in general, have not been designed using an understanding of how gel spreading govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels [2]. Here, we extend our initial analysis: we incorporate a yield stress, and we model the effects of gel dilution due to contact with vaginal fluid produced at the gel-tissue interface. Our model developed in [2] is supplemented with a convective-diffusive transport equation to characterize dilution, and solved using a multi-step scheme in a moving domain. The association between local dilution of gel and rheological properties is obtained experimentally. To model the common yield stress property of gels, we proceed by scaling analysis first. This establishes the conditions for validity of lubrication theory of a shear thinning yield stress fluid. This involves further development of the model in [2], incorporating a biviscosity model.[4pt] [1] Karim, et al., Science, 2010.[0pt] [2] Szeri, et al., Phy. of Fluids, 2008.

Antiviral and immunological effects of tenofovir microbicide in vaginal herpes simplex virus 2 infection.

PubMed

Vibholm, Line; Reinert, Line S; Søgaard, Ole S; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Melchjorsen, Jesper

2012-11-01

The anti-HIV microbicide, tenofovir (TFV) gel, has been shown to decrease HIV-1 acquisition by 39% and reduce herpes simplex virus 2 (HSV-2) transmission by 51%. We evaluated the effect of a 1% TFV gel on genital HSV-2 infection in a mouse vaginal challenge model. In vitro plaque assays and luminex multiplex bead analysis were used, respectively, to measure postinfection vaginal viral shedding (day 1) and cytokine secretion (day 2). To further investigate the anti-HSV-2 properties, we evaluated the direct antiviral effect of TFV and the oral prodrug tenofovir disoproxil fumerate (TDF) in cell culture. Compared to placebo-treated mice, TFV-treated mice had significantly lower clinical scores, developed later genital lesions, and showed reduced vaginal viral shedding. Furthermore, the levels of IFN-γ, IL-2, TNF-α, and other cytokines were altered in the vaginal fluid following topical tenofovir treatment and subsequent HSV-2 challenge. Finally, we found that both TFV and TDF inhibited HSV-2 infection in vitro; TDF showed a 50-fold greater potency than TFV. In conclusion, we confirmed that the microbicide TFV had direct anti-HSV-2 effects in a murine vaginal challenge model. Therefore, this model would be suitable for evaluating present and future microbicide candidates. Furthermore, the present study warrants further investigation of TDF in microbicides.

Early pregnancy vaginal microbiome trends and preterm birth.

PubMed

Stout, Molly J; Zhou, Yanjiao; Wylie, Kristine M; Tarr, Phillip I; Macones, George A; Tuuli, Methodius G

2017-09-01

Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions. To characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth. This is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term. A total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness

Progesterone Inhibition of Neuronal Calcium Signaling Underlies Aspects of Progesterone-Mediated Neuroprotection

PubMed Central

Luoma, Jessie I; Stern, Christopher M; Mermelstein, Paul G.

2011-01-01

Progesterone is being utilized as a therapeutic means to ameliorate neuron loss and cognitive dysfunction following traumatic brain injury Although there have been numerous attempts to determine the means by which progesterone exerts neuroprotective effects, studies describing the underlying molecular mechanisms are lacking What has become clear, however, is the notion that progesterone can thwart several physiological processes that are detrimental to neuron function and survival, including inflammation, edema, demyelination and excitotoxicity One clue regarding the means by which progesterone has restorative value comes from the notion that these aforementioned biological processes all share the common theme of eliciting pronounced increases in intracellular calcium. Thus, we propose the hypothesis that progesterone regulation of calcium signaling underlies its ability to mitigate these cellular insults, ultimately leading to neuroprotection. Further, we describe recent findings that indicate neuroprotection is achieved via progesterone block of voltage-gated calcium channels, although additional outcomes may arise from blockade of various other ion channels and neurotransmitter receptors. PMID:22101209

Obstetric gel shortens second stage of labor and prevents perineal trauma in nulliparous women: a randomized controlled trial on labor facilitation.

PubMed

Schaub, Andreas F; Litschgi, Mario; Hoesli, Irene; Holzgreve, Wolfgang; Bleul, Ulrich; Geissbühler, Verena

2008-01-01

To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum. A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited. A total of 228 eligible women were randomly assigned to Group A, without obstetric gel use, or to Group B, obstetric gel use, i.e., intermittent application into the birth canal during vaginal examinations, starting at the early first stage of labor (prior to 4 cm dilation) and ending with delivery. A total of 183 cases were analyzed. For vaginal deliveries without interventions, such as C-section, vaginal operative procedure or Kristeller maneuver, obstetric gel use significantly shortened the second stage of labor by 26 min (30%) (P=0.026), and significantly reduced perineal tears (P=0.024). First stage of labor and total labor duration were also shortened, but not significantly. Results did not show a significant change in secondary outcome parameters, such as intervention rates or maternal and newborn outcomes. No side effects were observed with obstetric gel use. Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity. Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameters.

Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus

PubMed Central

Mehta, Fabiola F.; Son, Jieun; Hewitt, Sylvia C.; Jang, Eunjung; Lydon, John P.; Korach, Kenneth S.; Chung, Sang-Hyuk

2016-01-01

While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor α (ERα) in the female reproductive tracts. Using knock−in mouse models expressing ERα mutants, we determined that the DNA−binding domain (DBD) and AF2 domain of ERα were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERα AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERα DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERα. Epithelial ERα was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus. PMID:27007157

Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus.

PubMed

Mehta, Fabiola F; Son, Jieun; Hewitt, Sylvia C; Jang, Eunjung; Lydon, John P; Korach, Kenneth S; Chung, Sang-Hyuk

2016-04-05

While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor α (ERα) in the female reproductive tracts. Using knock-in mouse models expressing ERα mutants, we determined that the DNA-binding domain (DBD) and AF2 domain of ERα were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERα AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERα DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERα. Epithelial ERα was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus.

Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain.

PubMed

Gómez-Camarillo, Madaí A; Beyer, Carlos; Lucio, Rosa Angélica; García-Juárez, Marcos; González-Arenas, Aliesha; Camacho-Arroyo, Ignacio; Komisaruk, Barry R; González-Flores, Oscar

2011-05-30

The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P. Copyright © 2011 Elsevier Inc. All rights reserved.

Progesterone-Mediated Non-Classical Signaling.

PubMed

Garg, Deepika; Ng, Sinnie Sin Man; Baig, K Maravet; Driggers, Paul; Segars, James

2017-09-01

Progesterone is essential for pregnancy maintenance and menstrual cycle regulation. Hormone action has been primarily ascribed to the well-characterized classical signaling pathway involving ligand binding, activation of nuclear progesterone receptors (PRs), and subsequent activation of genes containing progesterone response elements (PREs). Recent studies have revealed progesterone actions via non-classical signaling pathways, often mediated by non-genomic signaling. Progesterone signaling, in conjunction with growth factor signaling, impacts on the function of growth factors and regulates important physiological actions such as cell growth and remodeling, as well as apoptosis. This review focuses on non-classical progesterone signaling pathways, both including and excluding PR, and highlights how research in this area will provide a better understanding of progesterone actions and may inform novel therapeutic strategies. Copyright © 2017. Published by Elsevier Ltd.

21 CFR 556.540 - Progesterone.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Progesterone. 556.540 Section 556.540 Food and... Residues of New Animal Drugs § 556.540 Progesterone. (a) [Reserved] (b) Tolerances. Residues of progesterone are not permitted in excess of the following increments above the concentrations of progesterone...

21 CFR 556.540 - Progesterone.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Progesterone. 556.540 Section 556.540 Food and... Residues of New Animal Drugs § 556.540 Progesterone. (a) [Reserved] (b) Tolerances. Residues of progesterone are not permitted in excess of the following increments above the concentrations of progesterone...

21 CFR 556.540 - Progesterone.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Progesterone. 556.540 Section 556.540 Food and... Residues of New Animal Drugs § 556.540 Progesterone. (a) [Reserved] (b) Tolerances. Residues of progesterone are not permitted in excess of the following increments above the concentrations of progesterone...

Progesterone alters biliary flow dynamics.

PubMed

Tierney, S; Nakeeb, A; Wong, O; Lipsett, P A; Sostre, S; Pitt, H A; Lillemoe, K D

1999-02-01

To test the hypothesis that progesterone alters sphincter of Oddi and gallbladder function and, therefore, bile flow dynamics. Although the effects of progesterone on the biliary tract have been implicated in the increased incidence of gallstones among women, the specific effects of prolonged elevation of progesterone levels, such as occurs with contraceptive progesterone implants and during pregnancy, on the sphincter of Oddi and biliary flow dynamics are still incompletely understood. Adult female prairie dogs were randomly assigned to receive subcutaneous implants containing either progesterone or inactive pellet matrix only. Hepatic bile partitioning and gallbladder emptying were determined 14 days later using 99mTc-Mebrofenin cholescintigraphy. Significantly less hepatic bile partitioned into the gallbladder in progesterone-treated than in control animals. The gallbladder ejection fraction was significantly reduced from 73+/-6% in controls to 59+/-3% in the progesterone-treated animals. The rate of gallbladder emptying was significantly reduced from 3.6+/-0.3%/minute to 2.9+/-0.1%/minute. Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women.

Deep infiltrating endometriosis: Should rectal and vaginal opacification be systematically used in MR imaging?

PubMed

Uyttenhove, F; Langlois, C; Collinet, P; Rubod, C; Verpillat, P; Bigot, J; Kerdraon, O; Faye, N

2016-06-01

To evaluate the interest of rectal and vaginal filling in vaginal and recto-sigmoid endometriosis with MR imaging. To compare the results between a senior and a junior radiologist review. Sixty-seven patients with clinically suspected deep infiltrating endometriosis were included in our MRI protocol consisting of repeated T2-weigthed sequences (axial and sagittal) before and after rectal and vaginal marking with ultrasonography gel. Vaginal and recto-sigmoid endometriosis lesions were analyzed before and after opacification. The inter-reader agreement between senior and junior scores was studied. Concerning vaginal and muscularis and beyond colonic involvement, no significant difference (P=0.32) was observed and the inter-reader agreement was excellent (K=0.96 and 0.97 respectively). Concerning serosa colonic lesions, a significant difference was observed (P=0.01) and the inter-reader agreement was poor (K=0). Rectal and vaginal filling in endometriosis staging with MRI is not necessary no matter the reader experiment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Vaginal fold prolapse in a dog with pyometra and ovarian papillary cystadenocarcinoma.

PubMed

Zedda, Maria-Teresa; Bogliolo, Luisa; Ariu, Federica; Ledda, Mauro; Falchi, Laura; Pinna-Parpaglia, Maria-Luisa; Pau, Salvatore

2016-04-01

A 7-year-old 42-kg (92.4-lb) sexually intact nulliparous female Italian Mastiff was examined because of a history of vaginal prolapse during diestrus. A physical examination revealed vaginal fold prolapse. Abdominal ultrasonography revealed an enlarged uterus with hypoechogenic content, corpora lutea in the ovaries, and a cyst in the right ovary. Hematologic abnormalities included leukocytosis, neutrophilia, mild anemia, and low Hct. Progesterone and estradiol concentrations were 9.36 ng/mL and 30.42 pg/mL, respectively, in serum and 72.72 ng/mL and 792 pg/mL, respectively, in the ovarian cystic fluid. Ovariohysterectomy was performed; the prolapsed tissue was repositioned by external manipulation and maintained in situ by temporary apposition of the vulvar lips with a retention suture. Anatomic and histologic examinations of the excised tissues revealed pyometra and papillary cystadenocarcinoma in the right ovary. The vaginal hyperplasia completely regressed at 35 days after surgery; 5 months after surgery, the dog's general condition was considered good. Findings in this case were indicative of a hormonally active ovarian papillary cystadenocarcinoma in a female dog in diestrus. Hormone production by the cystadenocarcinoma was the predisposing factor that induced pyometra, mucosal hyperplasia, and vaginal fold prolapse in the dog. On the basis of these concurrent disorders, ovariohysterectomy was an appropriate treatment.

The value of oral micronized progesterone in the prevention of recurrent spontaneous preterm birth: a randomized controlled trial.

PubMed

Ashoush, Sherif; El-Kady, Osama; Al-Hawwary, Gehan; Othman, Ahmed

2017-12-01

Progesterone is becoming universally accepted for preventing recurrent spontaneous preterm delivery. There is, however, poor consensus on the effective types and doses of progesterone to be used. Despite the encouraging available research, the role of oral micronized progesterone has not yet been thoroughly investigated. We randomized 212 singleton pregnancies with past history of spontaneous preterm delivery at <37 weeks, into a progesterone group (receiving 100 mg oral micronized progesterone, six-hourly, starting at 14-18 weeks until 37 weeks or delivery) and an identical placebo group. The rate of spontaneous preterm delivery was the primary outcome. Secondary outcomes included gestational age at birth and admission to neonatal intensive care units. The progesterone group delivered at a later gestational age, and needed longer tocolysis-to-delivery intervals (35.4 weeks vs. 33.9 weeks, p = 0.01, and 87 days vs. 36 days, p < 0.001, respectively). The relative risk of spontaneous preterm delivery was 0.7 (95% confidence interval 0.54-0.92, p = 0.01), and the number needed-to-treat to prevent one case of spontaneous preterm delivery was 5 (95% confidence interval 3-20). The two groups had similar rates of operative delivery and postpartum complications. Progesterone was associated with mild maternal dizziness (29.1% vs. 9.8%, p = 0.002), somnolence (41.6% vs. 19.7%, p = 0.002), and vaginal dryness (20.8% vs. 8.7%, p = 0.03), lower neonatal mortality rates (7.3% vs. 25.2%, p < 0.001), and shorter neonatal intensive care unit admissions (p = 0.008). Oral micronized progesterone is effective in preventing spontaneous preterm delivery. The additional advantages of oral administration, affordability, and high safety profile make it worth recommending, at least for further research. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Progesterone and human cognition.

PubMed

Henderson, V W

2018-06-01

Progesterone is a neurosteroid and a neuroactive steroid, produced primarily by the corpus luteum and the placenta. In some animal models, progesterone affects cognitive performance, and its potential role in human cognition is especially germane to women. This role can be investigated through associations between peripheral concentrations of progesterone in blood or saliva and neuropsychological test results, through differences in cognitive profiles between women using menopausal hormone therapy with and without a progestogen, and through clinical trials. In naturally cycling reproductive-age women and pregnant women, there is no consistent relation between progesterone levels and cognition. In postmenopausal women within 6 years of menopause and not using hormone therapy, progesterone levels are positively associated with verbal memory and global cognition, but reported associations in older postmenopausal women are null. Some observational studies of postmenopausal women using hormone therapy raise concern of a small deleterious cognitive effect of progestogen (medroxyprogesterone acetate was most often reported in these studies), but this association may due to confounding factors. Small, short-term clinical trials of progesterone show no meaningful effect on cognition. The quality of evidence is low, but overall findings do not reveal consistent, clinically important effects of progesterone on cognitive function in women.

17-OH progesterone

MedlinePlus

17-hydroxyprogesterone; Progesterone - 17-OH ... A high level of 17-OH progesterone may be due to: Tumors of the adrenal gland Congenital adrenal hyperplasia (CAH) In infants with CAH, the 17-OHP level ranges ...

Qualitative Analysis of Sexually Experienced Adolescent Females: Attitudes about Vaginal Health

PubMed Central

Francis, Jenny K R; Fraiz, Lauren Dapena; Catallozzi, Marina; Rosenthal, Susan L

2016-01-01

Structured Abstract Study Objective To explore adolescent’s perceptions of vaginal health, practices, and vaginally-placed products. Design Semi-structured interviews were audio-recorded and transcribed until achieving theoretical saturation. Setting Adolescent medicine clinics in NYC. Participants Adolescent females (n = 22) who were sexually experienced, predominately Hispanic (73%) with a mean age of 17.7 years (range 15–20 years). Interventions None Main Outcome Measures Interviews assessed perspectives on vaginal health, specific vaginal hygiene practices and attitudes about vaginally-placed products (contraceptive rings, intrauterine devices (IUDs), and proposed multi-purpose technologies (MPTs) administered as ring or gel). The interviews were transcribed and coded for relevant themes. Results Overlapping themes included young women’s view of their vagina as a space that needed to be healthy for sexual partners and future fertility. The vagina could not be presumed to be healthy and conversations about vaginal health were limited to only include specific individuals. All reported a variety of practices to maintain their vaginal health, including showering 1 to 5 times a day and using soaps specifically for the vagina. Attitudes about vaginally-placed products revealed concerns about the sensory experience of having a product in the vagina, safety concerns and interest in the product’s objective (prevention of pregnancy or infection). Conclusions Adolescents have very specific views and practices about their vaginas. Clinicians should initiate conversations about vaginal health and hygiene with adolescents and focus on the normalcy of the vagina. Development of vaginally-placed products should focus on the sensory experience, safety and purpose of the product. PMID:27133374

Progesterone alters biliary flow dynamics.

PubMed Central

Tierney, S; Nakeeb, A; Wong, O; Lipsett, P A; Sostre, S; Pitt, H A; Lillemoe, K D

1999-01-01

OBJECTIVE: To test the hypothesis that progesterone alters sphincter of Oddi and gallbladder function and, therefore, bile flow dynamics. SUMMARY BACKGROUND DATA: Although the effects of progesterone on the biliary tract have been implicated in the increased incidence of gallstones among women, the specific effects of prolonged elevation of progesterone levels, such as occurs with contraceptive progesterone implants and during pregnancy, on the sphincter of Oddi and biliary flow dynamics are still incompletely understood. METHODS: Adult female prairie dogs were randomly assigned to receive subcutaneous implants containing either progesterone or inactive pellet matrix only. Hepatic bile partitioning and gallbladder emptying were determined 14 days later using 99mTc-Mebrofenin cholescintigraphy. RESULTS: Significantly less hepatic bile partitioned into the gallbladder in progesterone-treated than in control animals. The gallbladder ejection fraction was significantly reduced from 73+/-6% in controls to 59+/-3% in the progesterone-treated animals. The rate of gallbladder emptying was significantly reduced from 3.6+/-0.3%/minute to 2.9+/-0.1%/minute. CONCLUSIONS: Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women. Images Figure 1. Figure 2. Figure 3. Figure 4. PMID:10024101

Reproductive performance of seasonally anovular mixed-bred dairy goats induced to ovulate with a combination of progesterone and eCG or estradiol.

PubMed

Contreras-Villarreal, Viridiana; Meza-Herrera, César A; Rivas-Muñoz, Raymundo; Angel-Garcia, Oscar; Luna-Orozco, Juan R; Carrillo, Evaristo; Mellado, Miguel; Véliz-Deras, Francisco G

2016-06-01

Adult goats (n = 32) were randomly assigned to one of four treatments (n = 8, each): (i) progesterone (P4 ) + equine chorionic gonadotropin (eCG), treated with 25 mg progesterone intramuscularly (i.m.) + 250 IU eCG 24 h later; (ii) cronolone + eCG, treated with vaginal sponges - 20 mg cronolone × 7 days + 250 IU eCG at pessary removal; (ii) P4 + estradiol (E2 ), treated with 25 mg progesterone i.m. + 1 mg estradiol 24 h later; (iv) cronolone + E2 , treated with vaginal sponges - 20 mg cronolone × 7 days + 1 mg of estradiol i.m. at pessary removal. Goats were tested for estrus throughout the presence of a buck. Seven days prior and after treatment, an ovarian ultrasonographic scanning was performed to determine ovarian function and structures. An ultrasonographic pregnancy diagnosis was performed on day 30 post-service. In all groups, 100% estrus response was observed within 96 h post-treatment. While ovulation occurred in 100% of P4 + eCG and cronolone + eCG treated goats, the other groups only depicted 50% ovulatory activity (P < 0.05). Pregnancy rate was higher (P <0.05) in the P4 + eCG and cronolone + eCG groups (88 and 100%, respectively), compared with 38% in P4 + E2 and cronolone + E2 groups. The best treatments were those in which eCG was applied. The P4 + eCG treatment was a pessary-free, cheaper and effective protocol to induce ovulation in goats during the seasonal anovulatory period. © 2015 Japanese Society of Animal Science.

A rare case of primary amenorrhea with two etiologies, hypothalamic amenorrhea, transverse vaginal septum, and no hematocolpos.

PubMed

Ghaffari, Firouzeh; Keikha, Fatemeh; Arabipoor, Arezoo

2015-01-01

We reported a rare case of hypothalamic amenorrhea and transverse vaginal septum. A 28-year-old woman presented with primary amenorrhea and no complaint of abdominal pain. Laparoscopy revealed a small rudimentary uterus with streak ovaries and a vaginal pouch. The patient with diagnosis of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome was subjected to a vaginoplasty in another fertility center. In our institute, after two courses of estrogen and progesterone, sonography revealed hematocolpos, while, under anesthesia, transverse vaginal septum was resected. Hysteroscopy revealed normal uterine cavity. She became pregnant 5 months postoperatively with controlled ovarian stimulation (COS) in conjunction with intrauterine insemination, and she has two healthy babies now. This case highlights the importance of careful evaluation of all primary amenorrheas. Clinicians should be aware of presence of more than one etiology which causes atypical presentations and accomplishes a systematic strategy for the evaluation of amenorrhea potential to avoid long-term side effects of a misdiagnosis.

A Rare Case of Primary Amenorrhea with Two Etiologies, Hypothalamic Amenorrhea, Transverse Vaginal Septum, and No Hematocolpos

PubMed Central

Ghaffari, Firouzeh; Keikha, Fatemeh; Arabipoor, Arezoo

2015-01-01

We reported a rare case of hypothalamic amenorrhea and transverse vaginal septum. A 28-year-old woman presented with primary amenorrhea and no complaint of abdominal pain. Laparoscopy revealed a small rudimentary uterus with streak ovaries and a vaginal pouch. The patient with diagnosis of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome was subjected to a vaginoplasty in another fertility center. In our institute, after two courses of estrogen and progesterone, sonography revealed hematocolpos, while, under anesthesia, transverse vaginal septum was resected. Hysteroscopy revealed normal uterine cavity. She became pregnant 5 months postoperatively with controlled ovarian stimulation (COS) in conjunction with intrauterine insemination, and she has two healthy babies now. This case highlights the importance of careful evaluation of all primary amenorrheas. Clinicians should be aware of presence of more than one etiology which causes atypical presentations and accomplishes a systematic strategy for the evaluation of amenorrhea potential to avoid long-term side effects of a misdiagnosis. PMID:25785213

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

PubMed

Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E; Atik, Ruth Bender; Bloemenkamp, Kitty Wm; Brady, Rebecca; Briley, Annette; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin; Eapen, Abey; Essex, Holly; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Parrott, Steve; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Trépel, Dominic; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark David; Khalaf, Yacoub; Goddijn, Mariëtte; Regan, Lesley; Rai, Rajendra

2016-05-01

Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of

RECTAL-SPECIFIC MICROBICIDE APPLICATOR: EVALUATION AND COMPARISON WITH A VAGINAL APPLICATOR USED RECTALLY

PubMed Central

Carballo-Diéguez, Alex; Giguere, Rebecca; Dolezal, Curtis; Bauermeister, José; Leu, Cheng-Shiun; Valladares, Juan; Rohan, Lisa C.; Anton, Peter A.; Cranston, Ross D.; Febo, Irma; Mayer, Kenneth; McGowan, Ian

2014-01-01

An applicator designed for rectal delivery of microbicides was tested for acceptability by 95 young men who have sex with men, who self-administered 4mL of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24 of the participants self-administered rectally 4mL of tenofovir or placebo gel over 7 days using a vaginal applicator, and compared both applicators on a Likert scale of 1–10, with 10 the highest rating. Participants reported high likelihood to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p= ns). Those who tested both liked the vaginal applicator significantly more than the rectal applicator (7.8 vs. 5.2, p=0.003). Improvements in portability, conspicuousness, aesthetics, tip comfort, product assembly and packaging were suggested for both. This rectal-specific applicator was not superior to a vaginal applicator. While likelihood of future use is reportedly high, factors that decrease acceptability may erode product use over time in clinical trials. Further attention is needed to develop user-friendly, quick-acting rectal microbicide delivery systems. PMID:24858481

The impact of obstetric gel on the second stage of labor and perineal integrity: a randomized controlled trial.

PubMed

Ashwal, Eran; Aviram, Amir; Wertheimer, Avital; Krispin, Eyal; Kaplan, Boris; Hiersch, Liran

2016-09-01

Dianatal® is a bioadhesive gliding film which reduces the opposing force to vaginal childbirth. We aimed to investigate the safety, applicability, and impact of Dianatal® obstetric gel on second stage of labor and perineal integrity. Low-risk singleton pregnancies at term were prospectively enrolled. Eligible women were randomly assigned to either labor management without using obstetric gel, or labor management using intermittent application of obstetric gel into the birth canal during vaginal examinations, starting at active phase of labor (≥4 cm dilation). The primary measured outcome was the length of second stage of labor. Overall, 200 cases were analyzed. Demographic, obstetrical, and labor characteristics were similar between the groups. Neither adverse events nor maternal or neonatal side effects were observed. The mean lengths of the active and second stages of labor were comparable between the obstetric gel-treated and the control groups (157 versus 219 min and 48 versus 56 min, respectively). None of the women had grade III/IV perineal tears. Maternal and neonatal outcomes were not negatively influenced by using obstetric gel. No difference was found after sub-group analysis for spontaneous vaginal delivery. Dianatal® obstetric gel is safe in terms of maternal or neonatal use. Albeit a trend toward shorter labor stages using Dianatal® obstetric gel, no significant differences were noted among the groups. In order to further investigate the influence of the obstetric gel on labor stage interval, perineal integrity and maternal and neonatal outcomes, larger randomized clinical trials are needed to be carried out.

Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy?

PubMed

Tuntiviriyapun, P; Panyakhamlerd, K; Triratanachat, S; Chatsuwan, T; Chaikittisilpa, S; Jaisamrarn, U; Taechakraichana, N

2015-04-01

The primary objective of this study was to evaluate the correlation among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal atrophy. The secondary objective was to develop a new parameter to improve the correlation. A cross-sectional descriptive study. Naturally postmenopausal women aged 45-70 years with at least one clinical symptom of vaginal atrophy of moderate to severe intensity were included in this study. All of the objective parameters (vaginal atrophy score, vaginal pH, the number of lactobacilli, vaginal maturation index, and vaginal maturation value) were evaluated and correlated with vaginal atrophy symptoms. A new parameter of vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy symptoms II was analyzed for correlation with the objective parameters. A total of 132 naturally postmenopausal women were recruited for analysis. Vaginal pH was the only objective parameter found to have a weak correlation with vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal atrophy symptoms II parameter showed moderate correlation with vaginal pH (r = 0.356, p < 0.001) and a weak correlation with the vaginal atrophy score (r = 0.230, p < 0.001). History of sexual intercourse within 3 months was associated with a better correlation between vaginal atrophy symptoms and the objective parameters. Vaginal pH was significantly correlated with vaginal atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be better tools for clinical evaluation and future study of the vaginal ecosystem.

Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α.

PubMed

Pang, Yefei; Dong, Jing; Thomas, Peter

2015-05-15

Progesterone exerts beneficial effects on the human cardiovascular system by inducing rapid increases in nitric oxide (NO) production in vascular endothelial cells, but the receptors mediating these nongenomic progesterone actions remain unclear. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that progesterone binds to plasma membranes of HUVECs with the characteristics of membrane progesterone receptors (mPRs). The selective mPR agonist Org OD 02-0 had high binding affinity for the progesterone receptor on HUVEC membranes, whereas nuclear PR (nPR) agonists R5020 and medroxyprogesterone acetate displayed low binding affinities. Immunocytochemical and Western blot analyses confirmed that mPRs are expressed in HUVECs and are localized on their plasma membranes. NO levels increased rapidly after treatment with 20 nM progesterone, Org OD 02-0, and a progesterone-BSA conjugate but not with R5020, suggesting that this progesterone action is at the cell surface and initiated through mPRs. Progesterone and Org OD 02-0 (20 nM) also significantly increased endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation. Knockdown of mPRα expression by treatment with small-interfering RNA (siRNA) blocked the stimulatory effects of 20 nM progesterone on NO production and eNOS phosphorylation, whereas knockdown of nPR was ineffective. Treatment with PI3K/Akt and MAP kinase inhibitors blocked the stimulatory effects of progesterone, Org OD 02-0, and progesterone-BSA on NO production and eNOS phosphorylation and also prevented progesterone- and Org OD 02-0-induced increases in Akt and ERK phosphorylation. The results suggest that progesterone stimulation of NO production in HUVECs is mediated by mPRα and involves signaling through PI3K/Akt and MAP kinase pathways. Copyright © 2015 the American Physiological Society.

Qualitative Analysis of Sexually Experienced Female Adolescents: Attitudes about Vaginal Health.

PubMed

Francis, Jenny K R; Fraiz, Lauren Dapena; Catallozzi, Marina; Rosenthal, Susan L

2016-10-01

To explore adolescent's perceptions of vaginal health, practices, and vaginally-placed products. Semistructured interviews were audio-recorded and transcribed until theoretical saturation was achieved. Adolescent medicine clinics in New York City. Female adolescents (N = 22) who were sexually experienced, predominately Hispanic (73%, n = 16) with a mean age of 17.7 years (range, 15-20 years). None. Interviews were used to assess perspectives on vaginal health, specific vaginal hygiene practices, and attitudes about vaginally-placed products (contraceptive rings, intrauterine devices), and proposed multipurpose technologies administered as ring or gel). The interviews were transcribed and coded for relevant themes. Overlapping themes included young women's view of their vagina as a space that needed to be healthy for sexual partners and future fertility. The vagina could not be presumed to be healthy and conversations about vaginal health were limited to include only specific individuals. All reported a variety of practices to maintain their vaginal health, including showering 1-5 times a day and using soaps specifically for the vagina. Attitudes about vaginally-placed products revealed concerns about the sensory experience of having a product in the vagina, safety concerns and interest in the product's objective (prevention of pregnancy or infection). Adolescents have very specific views and practices about their vaginas. Clinicians should initiate conversations about vaginal health and hygiene with adolescents and focus on the normalcy of the vagina. Development of vaginally-placed products should focus on the sensory experience, safety, and purpose of the product. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Development of dapivirine vaginal ring for HIV prevention.

PubMed

Devlin, Bríd; Nuttall, Jeremy; Wilder, Susan; Woodsong, Cynthia; Rosenberg, Zeda

2013-12-01

In the continuing effort to develop effective HIV prevention methods for women, a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine is currently being tested in two safety and efficacy trials. This paper reviews dapivirine ring's pipeline development process, including efforts to determine safe and effective dosing levels as well as identify delivery platforms with the greatest likelihood of success for correct and consistent use. Dapivirine gel and other formulations were developed and tested in preclinical and clinical studies. Multiple vaginal ring prototypes were also tested, resulting in the current ring design as well as additional designs under consideration for future testing. Efficacy results from clinical trials are expected in 2015. Through ongoing consultations with national regulatory authorities, licensure requirements for dapivirine vaginal ring approval have been defined. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies," held in Arlington, Virginia on February 21-22, 2013. It forms part of a special supplement to Antiviral Research. Copyright © 2013 Elsevier B.V. All rights reserved.

Vaginal disorders.

PubMed

Soderberg, S F

1986-05-01

Chronic vaginitis is the most common vaginal disorder. Dogs with vaginitis show no signs of systemic illness but often lick at the vulva and have purulent or hemorrhagic vaginal discharges. Vaginitis is most commonly secondary to a noninfectious inciting factor such as congenital vaginal anomalies, clitoral hypertrophy, foreign bodies, trauma to the vaginal mucosa, or vaginal tumors. Inspection of the caudal vagina and vestibule both visually and digitally will often reveal the source of vaginal irritation. Vaginal cytology is used to establish the stage of the estrous cycle as well as distinguish uterine from vaginal sources of discharge. Vaginal cultures are used to establish the predominant offending organism associated with vaginal discharges and may be used as a guide for selection of a therapeutic agent. Vaginitis is best managed by removing the inciting cause and treating the area locally with antiseptic douches. Congenital malformations at the vestibulovaginal or vestibulovulvar junction may prevent normal intromission. Affected bitches may be reluctant to breed naturally because of pain. Such defects are detected best by digital examination. Congenital vaginal defects may be corrected by digital or surgical means. Prolapse of tissue through the lips of the vulva may be caused by clitoral hypertrophy, vaginal hyperplasia, or vaginal tumors. Enlargement of clitoral tissue is the result of endogenous or exogenous sources of androgens. Treatment of this condition includes removal of the androgen source and/or surgical removal of clitoral tissue. Vaginal hyperplasia is detected during proestrus or estrus of young bitches. Hyperplastic tissue will regress during diestrus. Tissue that is excessively traumatized and/or prolapse of the entire vaginal circumference may be removed surgically. Ovariohysterectomy may be used to prevent recurrence. Vaginal tumors are detected most often in older intact bitches. Such tumors are generally of smooth muscle or fibrous

FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration.

PubMed

Perioli, Luana; Ambrogi, Valeria; Pagano, Cinzia; Scuota, Stefania; Rossi, Carlo

2009-07-30

Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity. All polymer mixtures employed were used to prepare tablets with the compactness and hardness so as allow the application on vaginal mucosa. FG90C performances improved in particular when mixed to PVPK90 (1:1 ratio). This kind of delivery system is suitable for formulating MET for topical application representing a good alternative to traditional dosage forms for vaginal topical administration.

A Combination Microbicide Gel Protects Macaques Against Vaginal Simian Human Immunodeficiency Virus-Reverse Transcriptase Infection, But Only Partially Reduces Herpes Simplex Virus-2 Infection After a Single High-Dose Cochallenge

PubMed Central

Hsu, Mayla; Aravantinou, Meropi; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, Jose A.; Zydowsky, Thomas M.

2014-01-01

Abstract Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We previously established a rhesus macaque model of vaginal HSV-2 preexposure followed by cochallenge with HSV-2 and simian/human immunodeficiency virus-reverse transcriptase (SHIV-RT). Using this model, we showed that a gel containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new generation microbicides against both viruses, we first established dual infection after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques. All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV-RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and T cell responses were detected in some HSV-2-infected animals. To test a CG gel containing MIV-150 and zinc acetate (MZC), which provided naive animals full protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14 days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9 infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20% (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel-treated animals seroconverted, and only the CG controls had measurable HSV-2-specific T cell responses. This study shows the promise of MZC to prevent immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2 infection after exposure to a high-dose inoculum. Additionally, it demonstrates the potential of a macaque coinfection model to evaluate broad-spectrum microbicides. PMID:24117013

A combination microbicide gel protects macaques against vaginal simian human immunodeficiency virus-reverse transcriptase infection, but only partially reduces herpes simplex virus-2 infection after a single high-dose cochallenge.

PubMed

Hsu, Mayla; Aravantinou, Meropi; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa

2014-02-01

Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We previously established a rhesus macaque model of vaginal HSV-2 preexposure followed by cochallenge with HSV-2 and simian/human immunodeficiency virus-reverse transcriptase (SHIV-RT). Using this model, we showed that a gel containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new generation microbicides against both viruses, we first established dual infection after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques. All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV-RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and T cell responses were detected in some HSV-2-infected animals. To test a CG gel containing MIV-150 and zinc acetate (MZC), which provided naive animals full protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14 days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9 infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20% (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel-treated animals seroconverted, and only the CG controls had measurable HSV-2-specific T cell responses. This study shows the promise of MZC to prevent immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2 infection after exposure to a high-dose inoculum. Additionally, it demonstrates the potential of a macaque coinfection model to evaluate broad-spectrum microbicides.

Differences in the binding mechanism of RU486 and progesterone to the progesterone receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skafar, D.F.

1991-11-12

The binding mechanism of the antagonist RU486 to the progesterone receptor was compared with that of the agonists progesterone and R5020. Both progesterone and RU486 bound to the receptor with a Hill coefficient of 1.2, indicating the binding of each ligand is positive cooperative. However, when each ligand was used to compete with ({sup 3}H)progesterone for binding to the receptor at receptor concentrations near 8 nM, at which the receptor is likely a dimer, the competition curve for RU486 was significantly steeper than the curves for progesterone and R5020. This indicated that a difference in the binding mechanism of RU486more » and progesterone can be detected when both ligands are present. In contrast, at receptor concentrations near 1 nM, at which the receptor is likely a monomer, the competition curves for all three ligands were indistinguishable. These results indicate that RU486 and agonists have different binding mechanisms for the receptor and further suggest that this difference may be related to site-site interactions within the receptor.« less

Optimal imaging and analysis of human vaginal coating by drug delivery gels

PubMed Central

Henderson, Marcus H; Couchman, Grace M; Walmer, David K; Peters, Jennifer J; Owen, Derek H; Brown, Matthew A; Lavine, Michael L; Katz, David F

2007-01-01

Objective We used a new optical imaging technique to compare human intravaginal coating distributions of Conceptrol® and Advantage™. These gels are surrogates for future microbicidal gels, differing in molecular structures and biophysical properties. Methods For each protocol, a 3-mL gel bolus was inserted to the posterior fornix while the woman was in the supine position. She then either: (1) remained supine (10 min); or (2) sat up (1 min), stood up (1 min), sat down (1 min), and returned to supine for a net elapsed time of 10 min. The imaging device is sized/shaped like a phallus, and measurements while the device was inserted provide data that simulate peri-intromission coating. Results Coating by Advantage™ was more extensive and uniform than coating by Conceptrol®, with smaller bare spots of uncoated epithelium. Change in posture tended to increase extent and uniformity of coating, details differing between gels. Conclusions Results are consistent with predictions of mechanistic coating theory, using gel rheological data as inputs. PMID:17241845

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

PubMed

Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

2013-01-01

The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

PubMed

Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Variations in microbicide gel acceptability among young women in the USA and Puerto Rico

PubMed Central

Giguere, Rebecca; Carballo-Diéguez, Alex; Ventuneac, Ana; Mabragaña, Marina; Dolezal, Curtis; Chen, Beatrice A.; Kahn, Jessica A.; Zimet, Gregory D.; McGowan, Ian

2011-01-01

In a multi-site study of vaginal microbicide acceptability conducted with sexually active young women, quantitative assessments revealed significant differences in acceptability by site. Participants in Puerto Rico rated the gel more favourably than mainland US participants in terms of liking the gel and likelihood of future use. To explain these differences, we examined responses to qualitative behavioural assessments. Young women in the mainland USA associated gel leakage with uncomfortable sensations experienced during menstruation, while young women in Puerto Rico had positive associations of gel use with douching. These negative or positive associations affected assessments of the gel’s physical qualities. In addition, young women’s perceptions of primary partners’ support for microbicide use influenced sexual satisfaction with the gel and, ultimately, product acceptability. Finally, geographic HIV risk context contributed to heightened HIV risk perception, which influenced likelihood of future microbicide use, even for women in stated monogamous relationships. Future microbicide acceptability studies should take into account potential differences in acceptability by site such as HIV risk perception based on local HIV prevalence, popularity of vaginal hygiene products in a specific area, and male attitudes in different cultures concerning women’s use of HIV protection strategies. PMID:22084840

Partial protection against multiple RT-SHIV162P3 vaginal challenge of rhesus macaques by a silicone elastomer vaginal ring releasing the NNRTI MC1220.

PubMed

Fetherston, Susan M; Geer, Leslie; Veazey, Ronald S; Goldman, Laurie; Murphy, Diarmaid J; Ketas, Thomas J; Klasse, Per Johan; Blois, Sylvain; La Colla, Paolo; Moore, John P; Malcolm, R Karl

2013-02-01

The non-nucleoside reverse transcriptase inhibitor MC1220 has potent in vitro activity against HIV type 1 (HIV-1). A liposome gel formulation of MC1220 has previously been reported to partially protect rhesus macaques against vaginal challenge with a simian HIV (SHIV). Here, we describe the pre-clinical development of an MC1220-releasing silicone elastomer vaginal ring (SEVR), including pharmacokinetic (PK) and efficacy studies in macaques. In vitro release studies were conducted on SEVRs loaded with 400 mg of MC1220, using simulated vaginal fluid (SVF, n = 4) and 1 : 1 isopropanol/water (IPA/H(2)O, n = 4) as release media. For PK evaluation, SEVRs were inserted into adult female macaques (n = 6) for 30 days. Following a 1 week washout period, fresh rings were placed in the same animals, which were then challenged vaginally with RT-SHIV162P3 once weekly for 4 weeks. SEVRs released 1.66 and 101 mg of MC1220 into SVF and IPA/H(2)O, respectively, over 30 days, the differential reflecting the low aqueous solubility of the drug. In macaque PK studies, MC1220 was consistently detected in vaginal fluid (peak 845 ng/mL) and plasma (peak 0.91 ng/mL). Kaplan-Meier analysis over 9 weeks showed significantly lower infection rates for animals given MC1220-containing SEVRs than placebo rings (hazard ratio 0.20, P = 0.0037). An MC1220-releasing SEVR partially protected macaques from vaginal challenge. Such ring devices are a practical method for providing sustained, coitally independent protection against vaginal exposure to HIV-1.

Progesterone Impairs Social Recognition in Male Rats

PubMed Central

Auger, Catherine J.

2012-01-01

The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppresses AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependant behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment lead to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. PMID:22366506

Progesterone impairs social recognition in male rats.

PubMed

Bychowski, Meaghan E; Auger, Catherine J

2012-04-01

The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppress AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependent behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment leads to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Is human chorionic gonadotropin supplementation beneficial for frozen and thawed embryo transfer in estrogen/progesterone replacement cycles?: A randomized clinical trial.

PubMed

Shiotani, Masahide; Matsumoto, Yukiko; Okamoto, Eri; Yamada, Satoshi; Mizusawa, Yuri; Furuhashi, Kohyu; Ogata, Hiromi; Ogata, Seiji; Kokeguchi, Shoji

2017-04-01

Human chorionic gonadotropin (hCG) is used frequently for luteal support in fresh in vitro fertilization cycles as it induces progesterone secretion from the ovaries after oocyte retrieval and modulates the endometrium for implantation in fresh cycles. In contrast, hCG is not usually used for the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement cycles because ovulation is suppressed. However, several studies have shown that luteinizing hormone and hCG receptors are present in the human endometrium and that hCG can directly induce the decidualization of endometrial stromal cells in vitro. Thus, this study evaluated whether hCG supplementation can be beneficial for cryopreserved-thawed embryo transfer in estrogen/progesterone replacement cycles. One-hundred-and seventy-three cryopreserved-thawed embryo transfer cycles with estrogen/progesterone replacement were divided randomly into two groups. Transdermal oestradiol was used in combination with vaginal progesterone suppositories for HR. The embryo transfer was performed on day 17 and/or day 20 of the HR therapy cycle in both groups. In Group A, 3000 IU of hCG was administered on days 17, 20, and 23. In Group B, hCG was not used. There was no significant difference in the average age of the patients, the average number of previous assisted reproductive technology cycles, or the average number of embryo transfers between the two groups. The rates of pregnancy and implantation per embryo were 37.2% and 25.3%, respectively, in Group A and 35.6% and 21.7%, respectively, in Group B. The pregnancy and implantation rates were similar in both groups. Supplementation with hCG is not beneficial for cryopreserved-thawed embryo transfer in estrogen/progesterone replacement cycles.

Measuring Dilution of Microbicide Gels with Optical Imaging

PubMed Central

Drake, Tyler K.; Shah, Tejen; Peters, Jennifer J.; Wax, Adam; Katz, David F.

2013-01-01

We present a novel approach for measuring topical microbicide gel dilution using optical imaging. The approach compares gel thickness measurements from fluorimetry and multiplexed low coherence interferometry in order to calculate dilution of a gel. As a microbicide gel becomes diluted at fixed thickness, its mLCI thickness measurement remains constant, while the fluorimetry signal decreases in intensity. The difference between the two measurements is related to the extent of gel dilution. These two optical modalities are implemented in a single endoscopic instrument that enables simultaneous data collection. A preliminary validation study was performed with in vitro placebo gel measurements taken in a controlled test socket. It was found that change in slope of the regression line between fluorimetry and mLCI based measurements indicates dilution. A dilution calibration curve was then generated by repeating the test socket measurements with serial dilutions of placebo gel with vaginal fluid simulant. This methodology can provide valuable dilution information on candidate microbicide products, which could substantially enhance our understanding of their in vivo functioning. PMID:24340006

Toxic mechanisms of 3-monochloropropane-1,2-diol on progesterone production in R2C rat leydig cells.

PubMed

Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Su, Zhijian; Zhang, Qihao; Ou, Shiyi; Huang, Yadong

2013-10-16

3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been shown to impede the male reproductive function. However, its mechanism of action remains to be elucidated. In this study, the effects of 3-MCPD on progesterone production were investigated using R2C Leydig cells. 3-MCPD caused concentration-dependent inhibition of cell viability at the IC25, IC50, and IC75 levels of 1.027, 1.802, and 3.160 mM, respectively. Single cell gel/comet assay and atomic force microscopy assay showed that 3-MCPD significantly induced early apoptosis. In addition, 3-MCPD significantly reduced progesterone production by reducing the expression of cytochrome P450 side-chain cleavage enzyme, steroidogenic acute regulatory protein, and 3β-hydroxysteroid dehydrogenase in R2C cells. The change in steroidogenic acute regulatory protein expression was highly consistent with progesterone production. Furthermore, the mitochondrial membrane potential and cAMP significantly decreased.

Progesterone as a bone-trophic hormone.

PubMed

Prior, J C

1990-05-01

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency

Non-specific vaginitis or vaginitis of undetermined aetiology.

PubMed

Faro, S; Phillips, L E

1987-01-01

Vaginitis is a complex syndrome that is probably the most common outpatient disease seen by the gynaecologist. The specific aetiologies of vaginitis are many. One of the most common entities, however, is "non-specific vaginitis" which can be subdivided into: Gardnerella vaginitis, anaerobic vaginosis, and vaginitis of undetermined aetiology. The role of Gardnerella as a causative agent for vaginitis has been studied in depth but its specific role remains controversial. Anaerobic vaginosis can be diagnosed by noting on microscopic examination the presence of clue cells, free-floating bacteria and numerous white blood cells (WBC's). Culturing an aliquot of the vaginal discharge reveals a high number of anaerobes. In addition, this condition responds to antibiotics effective against anaerobes, e.g., metronidazole. Vaginitis of undetermined aetiology is more complex and is characterized by a purulent vaginal discharge, a pH of 4.0-4.6, numerous WBC's, and a high concentration of bacteria. The microbiology of this vaginitis includes many facultative Gram-negative rods and Gram-positive cocci. Anaerobes may be present but do not make up a large component of the endogenous microflora. This condition does not respond to the usual antibiotic therapies employed in treating bacterial vaginitis. Since this condition appears to be primarily an inflammatory reaction, it may be responsive to topical antiinflammatory agents such as benzydamine.

Vaginal cancer

MedlinePlus

Vaginal cancer; Cancer - vagina; Tumor - vaginal ... Most vaginal cancers occur when another cancer, such as cervical or endometrial cancer , spreads. This is called secondary vaginal cancer. Cancer ...

Advances in development, scale-up and manufacturing of microbicide gels, films, and tablets.

PubMed

Garg, Sanjay; Goldman, David; Krumme, Markus; Rohan, Lisa C; Smoot, Stuart; Friend, David R

2010-12-01

Vaginal HIV microbicides are topical, self administered products designed to prevent or significantly reduce transmission of HIV infection in women. The earliest microbicide candidates developed have been formulated as coitally dependent (used around the time of sex) gels and creams. All microbicide candidates tested in Phase III clinical trials, so far, have been gel products with non-specific mechanisms of action. However, recently, research is focusing on compounds containing highly potent and specific anti-retrovirals. These specific anti-retrovirals are being formulated as primary dosage forms such as vaginal gels or in alternative dosage forms such as fast dissolve films and tablets. Recent innovations also include development of combination products of highly active antiviral drugs such as reverse transcriptase inhibitors and entry inhibitors, which would theoretically be more effective and would reduce the possibility of drug resistance. In this article, an overview of recent advances in the microbicide gel, film, and tablet formulations and issues pertaining to scale-up, formulation, and evaluation challenges and regulatory guidelines have been presented. This article forms part of a special supplement covering presentations on gels, tablets, and films from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

Progesterone: The neglected hormone in schizophrenia? A focus on progesterone-dopamine interactions.

PubMed

Sun, Jeehae; Walker, Adam J; Dean, Brian; van den Buuse, Maarten; Gogos, Andrea

2016-12-01

Sex differences appear to be an important factor in schizophrenia. Women with schizophrenia tend to exhibit less disease impairment than men, typically presenting with a later age-at-onset, lower overall incidence and less severe symptoms. These observations underpin the estrogen hypothesis of schizophrenia, which postulates a protective role of estrogen against the development and severity of the disorder. While there has been significant attention placed on the impact of estrogens in schizophrenia, less consideration has been afforded to the role of progesterone, the other main female gonadal hormone. This narrative review discusses the role of progesterone as a neuroactive steroid and how it may be dysregulated in schizophrenia. Preclinical and molecular studies relevant to schizophrenia are discussed with a particular focus on the interactions between progesterone and the dopaminergic system. Notably, existing data on progesterone in relation to schizophrenia is inconsistent, with some studies suggesting a neuroprotective role for the hormone (e.g. animal models of cognitive dysfunction and positive symptoms), while other studies posit a disruptive impact of the hormone (e.g. negative correlations with symptom modulation in patients). This review aims to thoroughly address these discrepancies, concluding that altogether the data suggest that progesterone is a key modulator of central systems implicated in schizophrenia. On this basis, we argue that a more inclusive, considered effort of future studies to understand the intricacies of the interactions between progesterone and estrogen. Such an effort may enhance our understanding of the roles of sex hormones in schizophrenia, thus leading to avenues for novel therapeutic approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sustained release of the CCR5 inhibitors CMPD167 and maraviroc from vaginal rings in rhesus macaques.

PubMed

Malcolm, R Karl; Veazey, Ronald S; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M; Murphy, Diarmaid J; Boyd, Peter; Major, Ian; Shattock, Robin J; Klasse, Per Johan; Doyle, Lara A; Rasmussen, Kelsi K; Goldman, Laurie; Ketas, Thomas J; Moore, John P

2012-05-01

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

PubMed Central

Veazey, Ronald S.; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M.; Murphy, Diarmaid J.; Boyd, Peter; Major, Ian; Shattock, Robin J.; Klasse, Per Johan; Doyle, Lara A.; Rasmussen, Kelsi K.; Goldman, Laurie; Ketas, Thomas J.; Moore, John P.

2012-01-01

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ∼106-fold greater than the 50% inhibitory concentrations (IC50s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle. PMID:22330914

Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor.

PubMed

Veazey, Ronald S; Ketas, Thomas J; Dufour, Jason; Moroney-Rasmussen, Terri; Green, Linda C; Klasse, P J; Moore, John P

2010-09-01

An effective vaginal microbicide could reduce human immunodeficiency virus type 1 (HIV-1) transmission to women. Among microbicide candidates in clinical development is Maraviroc (MVC), a small-molecule drug that binds the CCR5 co-receptor and impedes HIV-1 entry into cells. Delivered systemically, MVC reduces viral load in HIV-1-infected individuals, but its ability to prevent transmission is untested. We have now evaluated MVC as a vaginal microbicide with use of a stringent model that involves challenge of rhesus macaques with a high-dose of a CCR5-using virus, SHIV-162P3. Gel-formulated, prescription-grade MVC provided dose-dependent protection, half-maximally at 0.5 mM (0.25 mg/mL). The duration of protection was transient; the longer the delay between MVC application and virus challenge, the less protection (half life of approximately 4 h). As expected, MVC neither protected against challenge with a CXCR4-using virus, SHIV-KU1, nor exacerbated postinfection viremia. These findings validate MVC development as a vaginal microbicide for women and should guide clinical programs.

Protection of rhesus macaques from vaginal infection by vaginally delivered Maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor

PubMed Central

Veazey, Ronald S.; Ketas, Thomas J.; Dufour, Jason; Moroney-Rasmussen, Terri; Green, Linda C.; Klasse, P.J.; Moore, John P.

2010-01-01

An effective vaginal microbicide could reduce human immunodeficiency virus type 1 (HIV-1) transmission to women. Among microbicide candidates in clinical development is Maraviroc (MVC), a small molecule drug that binds the CCR5 co-receptor and impedes HIV-1 entry into cells. Delivered systemically, MVC reduces viral load in HIV-1-infected people, but its ability to prevent transmission is untested. We have now evaluated MVC as a vaginal microbicide, using a stringent model involving challenge of rhesus macaques with a high-dose of a CCR5-using virus, SHIV-162P3. Gel-formulated, prescription-grade MVC provided dose-dependent protection, half-maximally at 0.5 mM (0.25 mg/ml). The duration of protection was transient; the longer the delay between MVC application and virus challenge, the less protection (T1/2 ~ 4 h). As expected, MVC neither protected against challenge with a CXCR4-using virus, SHIV-KU1, nor exacerbated post-infection viremia. These findings validate MVC development as a vaginal microbicide for women, and should guide clinical programs. PMID:20629537

Vaginal Atrophy

MedlinePlus

... an Endocrinologist Search Featured Resource Menopause Map™ View Vaginal Atrophy October 2017 Download PDFs English Editors Christine ... during this time, including vaginal dryness. What is vaginal atrophy? Vaginal atrophy (also referred to as vulvovaginal ...

Partial protection against multiple RT-SHIV162P3 vaginal challenge of rhesus macaques by a silicone elastomer vaginal ring releasing the NNRTI MC1220

PubMed Central

Fetherston, Susan M.; Geer, Leslie; Veazey, Ronald S.; Goldman, Laurie; Murphy, Diarmaid J.; Ketas, Thomas J.; Klasse, Per Johan; Blois, Sylvain; La Colla, Paolo; Moore, John P.; Malcolm, R. Karl

2013-01-01

Objectives The non-nucleoside reverse transcriptase inhibitor MC1220 has potent in vitro activity against HIV type 1 (HIV-1). A liposome gel formulation of MC1220 has previously been reported to partially protect rhesus macaques against vaginal challenge with a simian HIV (SHIV). Here, we describe the pre-clinical development of an MC1220-releasing silicone elastomer vaginal ring (SEVR), including pharmacokinetic (PK) and efficacy studies in macaques. Methods In vitro release studies were conducted on SEVRs loaded with 400 mg of MC1220, using simulated vaginal fluid (SVF, n = 4) and 1 : 1 isopropanol/water (IPA/H2O, n = 4) as release media. For PK evaluation, SEVRs were inserted into adult female macaques (n = 6) for 30 days. Following a 1week washout period, fresh rings were placed in the same animals, which were then challenged vaginally with RT-SHIV162P3 once weekly for 4 weeks. Results SEVRs released 1.66 and 101 mg of MC1220 into SVF and IPA/H2O, respectively, over 30 days, the differential reflecting the low aqueous solubility of the drug. In macaque PK studies, MC1220 was consistently detected in vaginal fluid (peak 845 ng/mL) and plasma (peak 0.91 ng/mL). Kaplan–Meier analysis over 9weeks showed significantly lower infection rates for animals given MC1220-containing SEVRs than placebo rings (hazard ratio 0.20, P = 0.0037). Conclusions An MC1220-releasing SEVR partially protected macaques from vaginal challenge. Such ring devices are a practical method for providing sustained, coitally independent protection against vaginal exposure to HIV-1. PMID:23109186

Progesterone suppresses triple-negative breast cancer growth and metastasis to the brain via membrane progesterone receptor α.

PubMed

Zhou, Li; Zhou, Wei; Zhang, Hongwei; Hu, Yan; Yu, Lei; Zhang, Yufei; Zhang, Yanli; Wang, Shuang; Wang, Peng; Xia, Wei

2017-09-01

Progesterone plays an important role in mammary epithelial cell proliferation and differentiation. Evidence from experimental and clinical studies indicates that progesterone is a risk factor for breast cancer under certain conditions through binding nuclear progesterone receptor (PR). These mechanisms, however, are not applicable to triple-negative breast cancer (TNBC) due to the lack of PR in these cancers. In this study, we demonstrate that membrane progesterone receptor α (mPRα) is expressed in TNBC tissues and the expression level of mPRα is negatively associated with the TNM stage. We found that progesterone suppressed the growth, migration and invasion of mPRα+ human TNBC cells in vitro, which was neither mediated by PR nor by PR membrane component 1 (PGRMCl). Notably, these effects exerted by progesterone were significantly blocked by shRNA specific to mPRα. Moreover, the knockdown of mPRα expression impaired the inhibitory effects of progesterone on mPRα+ tumor growth and metastasis in vivo. These data collectively indicate that progesterone suppresses TNCB growth and metastasis via mPRα, which provides evidence of the anti-neoplastic effects of progesterone-mPRα pathway in the treatment of human TNBC.

Vaginal health in contraceptive vaginal ring users - A review.

PubMed

Lete, Iñaki; Cuesta, María C; Marín, Juan M; Guerra, Sandra

2013-08-01

To provide an overview of the available data from clinical studies of vaginal conditions in women who use a vaginal ring as a contraceptive. A systematic review of the literature. Millions of women have already used the ethylene vinyl acetate vaginal ring that releases ethinylestradiol and etonogestrel for contraception. Because of its small size, more than four out of five women using the ring report that they do not feel it, even during sexual intercourse. No colposcopic or cytological changes have been observed in users, although approximately 10% have increased vaginal discharge. While in vitro studies have shown adhesion of Candida yeasts to the vaginal ring surface, clinical studies have not demonstrated a greater incidence of Candida infections compared to users of equivalent oral contraceptives. Some clinical studies suggest a lower incidence of bacterial vaginosis. No interaction exists between concomitant use of the vaginal ring and other drugs or products for vaginal use. The use of a contraceptive vaginal ring does not alter the vaginal ecosystem and therefore does not substantially affect vaginal health.

Dose-ranging phase 1 study of TMC120, a promising vaginal microbicide, in HIV-negative and HIV-positive female volunteers.

PubMed

Jespers, Vicky A; Van Roey, Jens M; Beets, Greet I; Buvé, Anne M

2007-02-01

To evaluate the short-term safety, tolerability, and systemic exposure of a vaginal microbicide gel containing the nonnucleoside reverse transcriptase inhibitor TMC120. Randomized, controlled, double-blind, phase 1 trial of a gel containing 3 different concentrations of TMC120 versus placebo. Of the 48 HIV-negative and 16 HIV-positive women enrolled, 52 women received active product. Participants applied the gel twice daily for 7 days and were assessed on 6 occasions. Colposcopic evaluation was performed before and after first gel application and on day 8. Laboratory safety assessments were carried out on all visits except day 7. Plasma levels of TMC120 were measured on days 1 and 7. All TMC120 concentrations were well tolerated, and there were no apparent differences in safety parameters. Four women (6%) had treatment-emergent mild cervical findings (petechiae in 3 women and erythema in 1 woman) of <5 mm. Plasma levels of TMC120 were quantifiable on day 1 in 7 (13%) participants and on day 7 in 39 (75%) participants using TMC120 gel. The TMC120 vaginal gel was well-tolerated in this short study by HIV-negative and HIV-positive women. The implications of the absorption of TMC120 should be studied further in expanded safety and effectiveness trials.

21 CFR 862.1620 - Progesterone test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Progesterone test system. 862.1620 Section 862....1620 Progesterone test system. (a) Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used...

21 CFR 862.1620 - Progesterone test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Progesterone test system. 862.1620 Section 862....1620 Progesterone test system. (a) Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used...

21 CFR 862.1620 - Progesterone test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Progesterone test system. 862.1620 Section 862....1620 Progesterone test system. (a) Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used...

Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

PubMed

Scavone, Cristina; Bonagura, Angela Colomba; Fiorentino, Sonia; Cimmaruta, Daniela; Cenami, Rosina; Torella, Marco; Fossati, Tiziano; Rossi, Francesco

2016-06-01

new formulation of progesterone was shown to be safe and not inferior to other products already on the market, with the exception of progesterone administered vaginally. As shown by the results of clinical studies presented in this review, the newly approved medicines containing cyclodextrins have been found to be as effective and as well-tolerated as other medicinal products that do not contain cyclodextrins. Moreover, the newly approved lower dose of diclofenac associated with cyclodextrins is consistent with the European Medicines Agency recommendations reported in the revision of the Assessment Report for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Cardiovascular Risk. Finally, the use of cyclodextrins led to significant increases in solubility and bioavailability of drugs, such as diclofenac and progesterone, and improvement in the efficacy and safety of these drugs.

Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

PubMed Central

Wang, Lin; Sassi, Alexandra Beumer; Patton, Dorothy; Isaacs, Charles; Moncla, B. J.; Gupta, Phalguni; Rohan, Lisa Cencia

2015-01-01

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae. PMID:22149387

Analysis of Vaginal Cell Populations during Experimental Vaginal Candidiasis

PubMed Central

Fidel, Paul L.; Luo, Wei; Steele, Chad; Chabain, Joseph; Baker, Marc; Wormley, Floyd

1999-01-01

Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leukocytes (PMN) had no effect on infection in the presence or absence of pseudoestrus. These results indicate a lack of demonstrable effects by systemic CMI or PMN against vaginitis and suggest that if local T cells are important, they are functioning without showing significant increases in numbers within the vaginal mucosa during infection. PMID:10338532

Vaginal Toxic Shock Reaction Triggering Desquamative Inflammatory Vaginitis

PubMed Central

Pereira, Nigel; Edlind, Thomas D.; Schlievert, Patrick M.; Nyirjesy, Paul

2012-01-01

Objective To report two cases of desquamative inflammatory vaginitis (DIV) associated with toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strains. Materials and Methods Case report of two patients, one with an acute and one with a chronic presentation, diagnosed with DIV on the basis of clinical findings and wet mount microscopy. Pre- and posttreatment vaginal bacterial and yeast cultures were obtained. Results Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial cultures following oral antibiotic therapy were negative. Conclusions DIV may be triggered through TSST-1-mediated vaginal toxic shock reaction. PMID:23222054

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes.

PubMed

Notario-Pérez, Fernando; Ruiz-Caro, Roberto; Veiga-Ochoa, María-Dolores

2017-01-01

Infection with human immunodeficiency virus (HIV) remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV.

Altrenogest and progesterone therapy during pregnancy in bottlenose dolphins (Tursiops truncatus) with progesterone insufficiency.

PubMed

Robeck, Todd R; Gill, Claudia; Doescher, Bethany M; Sweeney, Jay; De Laender, Piet; Van Elk, Cornelis E; O'Brien, Justine K

2012-06-01

Progesterone production is essential for growth and development of the conceptus during pregnancy. Abnormal development of the corpus luteum (CL) after conception can result in early embryonic loss or fetal abortion. Routine monitoring of bottlenose dolphin (Tursiops truncatus) pregnancy after artificial insemination or natural conception with ultrasonography and serum progesterone determination has allowed for the establishment of expected fetal growth rates and hormone concentrations. Using these monitoring techniques, we revealed four pregnant dolphins (12-24 yr old) with abnormally low progesterone production indicative of luteal insufficiency. Once diagnosed, animals were placed on altrenogest (0.044-0.088 mg/kg once daily) alone or with oral progesterone (50-200 mg twice daily). Doses of hormone were increased or decreased in each animal based on how fetal skull biparietal and thoracic growth rates compared with published normal values. Hormones were withdrawn starting from day 358 of gestation in animals 1 and 2, with labor occurring 6 and 7 days after withdrawal and at 376 and 373 days of gestation, respectively. Both deliveries were dystocic, with each calf requiring manual extraction and fetotomy for calf 1. The fetuses in animals 3 and 4 died at 348 and 390 days of gestation, respectively. Induction of labor was attempted in both animals, after fetal death, by using a combination of rapid progesterone withdrawal and steroid and prostaglandin F2alpha administration. The calf of animal 4 had to be removed with manual cervical dilation and fetotomy All adult females survived the procedures. These data provide the first in vivo evidence that the CL is the primary source of progesterone throughout pregnancy in the bottlenose dolphin. Until further characterization of hormones required during pregnancy and at parturition has been accomplished, the exogenous progestagen supplementation protocol described here cannot be recommended for treatment of progesterone

Relationship of Estimated SHIV Acquisition Time Points During the Menstrual Cycle and Thinning of Vaginal Epithelial Layers in Pigtail Macaques.

PubMed

Kersh, Ellen N; Ritter, Jana; Butler, Katherine; Ostergaard, Sharon Dietz; Hanson, Debra; Ellis, Shanon; Zaki, Sherif; McNicholl, Janet M

2015-12-01

HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P < 0.05, linear regression analysis), but not nucleated layer thinning (Pearson r = 0.6, P = 0.15). These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.

Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

PubMed

Thomas, Peter; Pang, Yefei

2013-06-01

The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation of a dye stain assay for vaginally inserted HEC-filled microbicide applicators

PubMed Central

Katzen, Lauren L.; Fernández-Romero, José A.; Sarna, Avina; Murugavel, Kailapuri G.; Gawarecki, Daniel; Zydowsky, Thomas M.; Mensch, Barbara S.

2011-01-01

Background The reliability and validity of self-reports of vaginal microbicide use are questionable given the explicit understanding that participants are expected to comply with study protocols. Our objective was to optimize the Population Council's previously validated dye stain assay (DSA) and related procedures, and establish predictive values for the DSA's ability to identify vaginally inserted single-use, low-density polyethylene microbicide applicators filled with hydroxyethylcellulose gel. Methods Applicators, inserted by 252 female sex workers enrolled in a microbicide feasibility study in Southern India, served as positive controls for optimization and validation experiments. Prior to validation, optimal dye concentration and staining time were ascertained. Three validation experiments were conducted to determine sensitivity, specificity, negative predictive values and positive predictive values. Results The dye concentration of 0.05% (w/v) FD&C Blue No. 1 Granular Food Dye and staining time of five seconds were determined to be optimal and were used for the three validation experiments. There were a total of 1,848 possible applicator readings across validation experiments; 1,703 (92.2%) applicator readings were correct. On average, the DSA performed with 90.6% sensitivity, 93.9% specificity, and had a negative predictive value of 93.8% and a positive predictive value of 91.0%. No statistically significant differences between experiments were noted. Conclusions The DSA was optimized and successfully validated for use with single-use, low-density polyethylene applicators filled with hydroxyethylcellulose (HEC) gel. We recommend including the DSA in future microbicide trials involving vaginal gels in order to identify participants who have low adherence to dosing regimens. In doing so, we can develop strategies to improve adherence as well as investigate the association between product use and efficacy. PMID:21992983

In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

PubMed

Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

2012-11-01

In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Vaginal Atrophy

MedlinePlus

... syndrome of menopause (GSM) increases your risk of: Vaginal infections. Changes in the acid balance of your vagina makes vaginal infections (vaginitis) more likely. Urinary problems. Urinary changes associated ...

What do Portuguese Women Prefer Regarding Vaginal Products? Results from a Cross-Sectional Web-Based Survey

PubMed Central

Palmeira-de-Oliveira, Rita; Duarte, Paulo; Palmeira-de-Oliveira, Ana; das Neves, José; Amaral, Maria Helena; Breitenfeld, Luiza; Martinez-de-Oliveira, José

2014-01-01

Therapeutic outcomes of vaginal products depend not only on their ability to deliver drugs to or through the vagina but also on acceptability and correct use. Women’s preferences, in turn, may vary according to age and cultural backgrounds. In this work, an anonymous online survey was completed by 2529 Portuguese women to assess their preferences for physical characteristics and mode of application of vaginal products, according to age. Additionally, intention to use and misconceptions about these issues were assessed. The majority of women of all age groups would use vaginal products to treat or prevent diseases, upon medical prescription. Women preferred vaginal products to be odorless and colorless gels, creams and ointments composed by natural origin drugs/excipients and applied by means of an applicator. Although the majority of women would prefer not to insert any product in the vagina, intention to use for self and recommendation to use for others was associated with previous experiences with vaginal products. General concerns and misconceptions related to use of vaginal products were rare. These data may contribute to the development of products that women are more prone to use. PMID:25337676

“Tell Juliana”: Acceptability of the Candidate Microbicide VivaGel® and Two Placebo Gels Among Ethnically Diverse, Sexually Active Young Women Participating in a Phase 1 Microbicide Study

PubMed Central

Giguere, Rebecca; Dolezal, Curtis; Chen, Beatrice A.; Kahn, Jessica; Zimet, Greg; Mabragaña, Marina; Leu, Cheng-Shiun; McGowan, Ian

2011-01-01

This study assessed acceptability of the candidate microbicide VivaGel® and two placebo gels among 61 sexually active young US and Puerto Rican women at three sites. Participants were randomly assigned to use one of the gels twice per day for 14 days. At trial completion, 59% of the women in the VivaGel® group reported being likely to use the gel in the future, whereas 23% were unlikely to use it and 18% were undecided. Participants reported problems with all three gels, including the “universal” placebo containing hydroxyethyl cellulose (HEC). The most frequent complaints were leakage, interference with sexual behavior, and decreased sexual satisfaction. Some of the complaints are not new but remain unresolved. Women’s perceived risk of HIV infection may determine whether the gels are used. Users also may want a choice of viscosity. Poor acceptability of vaginal microbicide formulations may result in poor adherence to gel use during efficacy trials and compromise validity of results. PMID:21863338

Progesterone resistance in endometriosis: origins, consequences and interventions.

PubMed

Patel, Bansari G; Rudnicki, Martin; Yu, Jie; Shu, Yimin; Taylor, Robert N

2017-06-01

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment. © 2017 Nordic Federation of

Physiology, production and action of progesterone.

PubMed

Taraborrelli, Stefania

2015-11-01

The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland, cardiovascular system, central nervous system and bones. In the last decades, the interest of researchers has focused on the role of progesterone in genomic and non-genomic receptor mechanisms. We searched PubMed up to December 2014 for publications on progesterone/steroidogenesis. A better understanding of the biological genomic and non-genomic receptor mechanisms could enable us in the near future to obtain a more comprehensive knowledge of the safety and efficacy of this agent during hormone replacement therapy (natural progesterone), in vitro fertilization (water-soluble subcutaneous progesterone), in traumatic brain injury, Alzheimer's disease and diabetic neuropathy, even though further clinical studies are needed to prove its usefulness. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Membrane progesterone receptors in reproduction and cancer.

PubMed

Valadez-Cosmes, Paulina; Vázquez-Martínez, Edgar Ricardo; Cerbón, Marco; Camacho-Arroyo, Ignacio

2016-10-15

Progesterone is a sexual steroid hormone that has a critical role in reproductive processes in males and females of several species, including humans. Furthermore, progesterone has been associated with pathological diseases such as breast, gynecological and brain cancer, regulating cell proliferation, apoptosis, and metastasis. In the past, progesterone actions were thought to be only mediated by its intracellular receptor (PR). However, recent evidence has demonstrated that membrane progesterone receptors (mPRs) mediate most of the non-classical progesterone actions. The role of the different mPRs subtypes in progesterone effects in reproduction and cancer is an emerging and exciting research area. Here we review studies to date regarding mPRs role in reproduction and cancer and discuss their functions and clinical relevance, suggesting mPRs as putative pharmacological targets and disease markers in cancer and diseases associated with reproduction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emphysematous vaginitis.

PubMed

Lima-Silva, Joana; Vieira-Baptista, Pedro; Cavaco-Gomes, João; Maia, Tiago; Beires, Jorge

2015-04-01

Emphysematous vaginitis is a rare condition, characterized by the presence of multiple gas-filled cysts in the vaginal and/or exocervical mucosa. Although its etiology is not completely understood, it is self-limited, with a benign clinical course. Vaginal discharge, sometimes bloody, and pruritus are the most common symptoms. Chronic and acute inflammation can be found, and diseases that impair the immune system and pregnancy have been associated with this condition. A 48-year-old postmenopausal woman, with a history of hysterectomy with several comorbidities, presented with a 4-month history of bloody discharge and vulvar pruritus. Examination showed multiple cystic lesions, 1 to 5 mm, occupying the posterior and right lateral vaginal walls. Speculum examination produced crepitus. Vaginal wet mount was normal, except for diminished lactobacilli; results of Trichomonas vaginalis DNA test and vaginal cultures were negative. Lugol's iodine applied to the vagina was taken up by the intact lesions. Biopsy result showed typical features of emphysematous vaginitis. This is an unusual entity, presenting with common gynecological complaints, and both physicians and pathologists should be aware to prevent misdiagnosis and overtreatment.

Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.

PubMed

Bender Ignacio, Rachel A; Perti, Tara; Magaret, Amalia S; Rajagopal, Sharanya; Stevens, Claire E; Huang, Meei-Li; Selke, Stacy; Johnston, Christine; Marrazzo, Jeanne; Wald, Anna

2015-12-15

Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear. We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates. 64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL. Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions. NCT01448616. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury

PubMed Central

Robertson, Courtney L.; Fidan, Emin; Stanley, Rachel M.; MHSA; Noje, Corina; Bayir, Hülya

2016-01-01

Objective To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury (TBI), and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric TBI. Data Sources National Library of Medicine PubMed literature review. Data Selection The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of TBI are summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult TBI is reviewed. Data Extraction and Synthesis Progesterone is a pleotropic agent with beneficial effects on secondary injury cascades that occur after TBI, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after TBI in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human Phase II trials of progesterone for adult TBI have been published, and two multi-center Phase III trials are underway. Conclusions The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of TBI. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children, and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, statue epilepticus). PMID

Does progesterone improve outcome in diffuse axonal injury?

PubMed

Soltani, Zahra; Shahrokhi, Nader; Karamouzian, Saeed; Khaksari, Mohammad; Mofid, Behshad; Nakhaee, Nouzar; Reihani, Hamed

2017-01-01

The benefits of progesterone have been demonstrated in the animal models of traumatic brain injury (TBI). However, the results of clinical studies are conflicting. Considering the heterogenic nature of TBI, the effect of progesterone in patients with diffuse axonal injury (DAI) was investigated in a clinical trial. In this study, 48 patients with DAI and Glasgow Coma Scale of 3-12, admitted within 4 hours after injury, were randomly assigned to the progesterone or control group. The dose of progesterone administration was 1 mg kg -1 per 12 hours for 5 days. The effect of progesterone was investigated using extended-Glasgow Outcome Scale (GOS-E), functional independence measure (FIM) scores and also mortality within the follow-up period. The progesterone group exhibited higher GOS-E and FIM scores in comparison to the control group at 6 months post-injury (p < 0.01 and p < 0.05, respectively). Mortality was also found in the control group (p < 0.05). The adverse events attributed to the progesterone administration were not found throughout the study. Findings of this study suggest that progesterone may be neuroprotective in patients with DAI. However, large clinical trials are needed to assess progesterone as a promising drug in DAI.

Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report.

PubMed

Godbole, Mukul; Tiwary, Kanishka; Badwe, Rajendra; Gupta, Sudeep; Dutt, Amit

2017-08-01

Pre-operative progesterone treatment of breast cancer has been shown to confer survival benefits to patients independent of their progesterone receptor (PR) status. The underlying mechanism and the question whether such an effect can also be observed in PR negative breast cancer cells remain to be resolved. We performed proteome profiling of PR-positive and PR-negative breast cancer cells in response to progesterone using a phospho-kinase array platform. Western blotting was used to validate the results. Cell-based phenotypic assays were conducted using PR-positive and PR-negative breast cancer cells to assess the effect of progesterone. We found that progesterone induces de-phosphorylation of 12 out of 43 kinases tested, which are mostly involved in cellular invasion and migration regulation. Consistent with this observation, we found through cell-based phenotypic assays that progesterone inhibits the invasion and migration of breast cancer cells independent of their PR status. Our results indicate that progesterone can inhibit breast cancer cell invasion and migration mediated by the de-phosphorylation of kinases. This inhibition appears to be independent of the PR status of the breast cancer cells. In a broader context, our study may provide a basis for an association between progesterone treatment and recurrence reduction in breast cancer patients, thereby providing a lead for modelling a randomized in vitro study.

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes

PubMed Central

Notario-Pérez, Fernando; Ruiz-Caro, Roberto; Veiga-Ochoa, María-Dolores

2017-01-01

Infection with human immunodeficiency virus (HIV) remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV. PMID:28670111

Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate (17-OHPC), and related progestins

PubMed Central

Attardi, Barbara J.; Zeleznik, Anthony; Simhan, Hyagriv; Chiao, Jye Ping; Mattison, Donald R; Caritis, Steve N

2007-01-01

Condensation 17-hydroxyprogesterone caproate is not better than progesterone in binding to progesterone or glucocorticoid receptors or eliciting gene expression in progesterone responsive genes. Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate (17-OHPC), and related progestins. Objective To determine whether the reduction in premature birth attributable to 17-OHPC occurs because of a greater affinity for progesterone (PR) or glucocorticoid (GR) receptors or by enhanced stimulation of progestogen responsive genes when compared with progesterone. Study Design We performed competitive steroid hormone receptor binding assays using cytosols expressing either recombinant human PR-A (rhPR-A) or B (rhPR-B) or rabbit uterine or thymic cytosols. We used four different carcinoma cell lines to assess transactivation of reporter genes or induction of alkaline phosphatase. Results Relative binding affinity of 17-OHPC for rhPR-B, rhPR-A and rabbit PR was 26–30% that of progesterone. Binding of progesterone to rabbit thymic GR was weak. 17-OHPC was comparable to progesterone in eliciting gene expression in all cell lines studied. Conclusions Binding to PR, GR or expression of progesterone-responsive genes is no greater with 17-OHPC than with progesterone. Other mechanisms must account for the beneficial effect of 17-OHPC on preterm birth rates. PMID:18060946

Autoimmune progesterone dermatitis.

PubMed

Detrixhe, A; Nikkels, A F; Dezfoulian, B

2017-11-01

Autoimmune progesterone dermatitis (APD) is an exceptional condition affecting young women of childbearing age with a high prevalence during the third decade of life. The diagnosis should be confirmed using an intradermal skin test to progesterone, during the follicular phase of the menstrual cycle. APD represents an early manifestation of autoimmune disease. A case of APD is presented who after curative treatment did not develop other autoimmune diseases during a 6-year follow-up. Dermatologists, gynecologists and obstetricians should be aware of this rare but highly invalidating entity.

Preferred Physical Characteristics of Vaginal Film Microbicides for HIV Prevention in Pittsburgh Women

PubMed Central

Fan, Maria D.; Kramzer, Lindsay F.; Hillier, Sharon L.; Chang, Judy C.; Meyn, Leslie A.; Rohan, Lisa C.

2016-01-01

Unprotected heterosexual intercourse is the leading cause of HIV acquisition in women. Due to the complex nature of correct and consistent condom use by both men and women, developing alternative female-controlled HIV prevention options is a global health priority. Vaginal films containing antiretroviral drugs are a potential delivery system for the prevention of HIV acquisition through sexual contact. In this study, we explored women’s preferences regarding physical characteristics of microbicide vaginal films through questionnaires and focus groups. Eighty-four sexually active, ethnically diverse women 18 to 30 years of age from Pittsburgh, Pennsylvania, participated in the study. Women visually and manually examined a variety of vaginal films, as well as three other vaginal products undergoing evaluation for HIV prevention: tablet, ring, and gel. Means and standard deviations or frequencies and 95% confidence intervals were calculated for questionnaire data. Focus groups were audio-recorded, transcribed verbatim, and coded for content analysis. Women most frequently preferred vaginal films to be smooth and thin (63%), translucent (48%), and 2"×2" square size (36%). Driving these preferences were five major themes: ease and accuracy of use, desire for efficacy, discretion, intravaginal comfort and minimal impact, and minimizing disruption of sexual mood/activities. Women’s preferences for various microbicide vaginal film physical attributes represented a balance of multiple values. In general, women desired a comfortable, efficacious, easy-to-use, and minimally intrusive product. PMID:27571742

Preferred Physical Characteristics of Vaginal Film Microbicides for HIV Prevention in Pittsburgh Women.

PubMed

Fan, Maria D; Kramzer, Lindsay F; Hillier, Sharon L; Chang, Judy C; Meyn, Leslie A; Rohan, Lisa C

2017-05-01

Unprotected heterosexual intercourse is the leading cause of HIV acquisition in women. Due to the complex nature of correct and consistent condom use by both men and women, developing alternative female-controlled HIV prevention options is a global health priority. Vaginal films containing antiretroviral drugs are a potential delivery system for the prevention of HIV acquisition through sexual contact. In this study, we explored women's preferences regarding physical characteristics of microbicide vaginal films through questionnaires and focus groups. Eighty-four sexually active, ethnically diverse women 18-30 years of age from Pittsburgh, Pennsylvania, participated in the study. Women visually and manually examined a variety of vaginal films, as well as three other vaginal products undergoing evaluation for HIV prevention: tablet, ring, and gel. Means and standard deviations or frequencies and 95 % confidence intervals were calculated for questionnaire data. Focus groups were audio-recorded, transcribed verbatim, and coded for content analysis. Women most frequently preferred vaginal films to be smooth and thin (63 %), translucent (48 %), and 2″ × 2″ square size (36 %). Driving these preferences were five major themes: ease and accuracy of use, desire for efficacy, discretion, intravaginal comfort and minimal impact, and minimizing disruption of sexual mood/activities. Women's preferences for various microbicide vaginal film physical attributes represented a balance of multiple values. In general, women desired a comfortable, efficacious, easy to use, and minimally intrusive product.

Epidemiological Investigation of Vaginal Saccharomyces cerevisiae Isolates by a Genotypic Method

PubMed Central

McCullough, Michael J.; Clemons, Karl V.; Farina, Claudio; McCusker, John H.; Stevens, David A.

1998-01-01

Saccharomyces cerevisiae is a ubiquitous, ascomycetous yeast, and vaginitis caused by this organism has been reported only very rarely. The aim of the present investigation was to assess the epidemiological relatedness of a group of vaginal and commercial S. cerevisiae isolates by a previously reported genetic typing method, which divided the isolates into two broad groups with numerous subtypes. Nineteen S. cerevisiae isolates obtained from patients suffering from vaginitis and four isolates from commercial products in the same city were analyzed. The cellular DNA from each isolate was digested with the restriction endonuclease EcoRI, and restriction fragment length polymorphisms were generated by horizontal gel electrophoresis. The results showed that although vaginal isolates did not cluster in any particular genetic subtype, multiple patients were infected with indistinguishable strains (there were nine distinct strains among 23 isolates). For two of three patients, all three with two episodes of S. cerevisiae vaginitis, different strains were isolated during the recurrence of this disease. Three other patients with indistinguishable isolates were epidemiologically related in that two were practitioners in the same clinic and the third was a patient at this clinic. We also found that one commercial strain was indistinguishable from the strain isolated from three different women at the time that they were suffering from vaginitis. The findings of the present study suggest that some S. cerevisiae strains may possess properties permitting persistence in the human host. Furthermore, person-to-person contact and the proliferation of the use of S. cerevisiae as a health-food product, in home baking, and in home brewing may be a contributing factor in human colonization and infection with this organism. PMID:9466776

Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome.

PubMed

Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E

2017-10-01

Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

Vaginal Cancer Overview

MedlinePlus

... are here Home > Types of Cancer > Vaginal Cancer Vaginal Cancer This is Cancer.Net’s Guide to Vaginal Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Vaginal Cancer Introduction Statistics Medical Illustrations Risk Factors and ...

Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis.

PubMed

Kaambo, Evelyn; Africa, Charlene; Chambuso, Ramadhani; Passmore, Jo-Ann Shelley

2018-01-01

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial "health" in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery.

Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis

PubMed Central

Kaambo, Evelyn; Africa, Charlene; Chambuso, Ramadhani; Passmore, Jo-Ann Shelley

2018-01-01

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial “health” in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery. PMID:29632854

Restraint Stress Inhibits Mouse Implantation: Temporal Window and the Involvement of HB-EGF, Estrogen and Progesterone

PubMed Central

Yuan, Hong-Jie; Liang, Bo; Zheng, Liang-Liang; Liu, Yu-Xiang; Luo, Ming-Jiu; Tan, Jing-He

2013-01-01

It is known that psychological stress affects reproduction in women, but it is unknown whether the effect is by impairing implantation. Although studies suggest that long periods of auditory or restraint stress may inhibit implantation in rats and mice, the exact stage of pregnancy at which stress impairs implantation is unclear. Furthermore, whether stress impairs implantation by decreasing the heparin-binding epidermal growth factor-like growth factor (HB-EGF), estrogen and/or progesterone and whether by acting on embryos or on the uterus need further investigations. In this study, a 24-h restraint stress was initiated at 15:30 of day 3 (regimen 1) or at 07:30 (regimen 2) or 15:30 of day 4 (regimen 3) of pregnancy (vaginal plug  =  day 1) to observe effects of restraint stress applied at different peri-implantation stages on implantation. Among the three regimens, whereas regimens 1 and 3 affected neither term pregnancy nor litter size, regimen 2 reduced both. Further observations indicated that regimen 2 of restraint stress also delayed blastocyst hatching and the attachment reaction, decreased serum concentrations of progesterone and estradiol, and down regulated the expression of HB-EGF in both the endometrium and blastocysts. Taken together, the results suggested that restraint stress inhibited mouse implantation in a temporal window-dependent manner and by impairing blastocyst activation and hatching and uterine receptivity via down-regulating HB-EGF, estrogen and progesterone. Thus, the stress applied within the implantation window impaired implantation by acting on both embryos and the uterus. PMID:24244689

Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.

PubMed

Anukam, Kingsley C; Osazuwa, Emmanuel; Osemene, Gibson I; Ehigiagbe, Felix; Bruce, Andrew W; Reid, Gregor

2006-10-01

Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.

Vaginal birth after cesarean section: an update on physician trends and patient perceptions.

PubMed

Penso, C

1994-10-01

The increased number of women having a vaginal birth after a cesarean section can be attributed to changing physician trends. Women eligible for vaginal birth after cesarean section include those with previous low vertical incisions, multiple previous incisions and even unknown scars, regardless of the method of closure or previous indication. Limited data suggest that in carefully selected women a current twin gestation, breech presentation, or the presence of fetal macrosomia are not contraindications for a trial of labor, in the presence of a uterine scar. Changing trends in the management of labor may also contribute to an increase in successful trial of labor with the use of oxytocin for the induction or augmentation of labor, the administration of epidural anesthesia for pain relief, and the instillation of prostaglandin E2 gel for cervical ripening. External cephalic version and amnioinfusion may also be reasonable alternatives in appropriately selected cases. Despite the documented safety and success of vaginal birth after cesarean section, and the lack of increased morbidity of failed trial of labor, 50% of women who are eligible for vaginal birth after cesarean section will decline an attempt, even after extensive counseling and encouragement. Patient resistance, largely attributed to the fear and inconvenience of labor, is still a major deterrent to a further rise in vaginal birth after cesarean section rates.

Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets.

PubMed

Panay, Nick; Maamari, Ricardo

2012-03-01

Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.

Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles.

PubMed

Papaleo, Enrico; Corti, Laura; Vanni, Valeria Stella; Pagliardini, Luca; Ottolina, Jessica; De Michele, Francesca; La Marca, Antonio; Viganò, Paola; Candiani, Massimo

2014-07-01

Modest increases of serum progesterone at human chorionic gonadotrophin (hCG) administration in controlled ovarian hyperstimulation (COH) cycles have been shown to have a negative impact on pregnancy outcomes. The aim of this study was to identify early predictors of progesterone elevation at hCG. Pregnancy outcome of 303 consecutive patients undergoing COH and fresh day-3 embryo transfer was analysed. Considering the non-linear relationship between progesterone at hCG triggering and pregnancy outcomes, partial area under the curve (pAUC) analysis was used to implement marker identification potential of receiver operating characteristic (ROC) curve analysis. Multivariate logistic analysis was then performed to identify predictors of progesterone rise. Pregnancy outcomes could be predicted by pAUC analysis (pAUC = 0.58, 95 % CI 0.51-0.66, p = 0.02) and a significant detrimental cut-off could be calculated (progesterone at hCG > 1.35 ng/ml). Total dose of rFSH administered, E2 level at hCG but mostly basal progesterone level (OR = 12.21, 95 % CI 1.82-81.70) were predictors of progesterone rise above the cut-off. Basal progesterone is shown to be the main prognostic factor for progesterone elevation. This observation should be taken into consideration in the clinical management of IVF/ICSI cycles to improve pregnancy outcomes.

Premenarchal, recurrent vaginal discharge associated with an incomplete obstructing longitudinal vaginal septum.

PubMed

Hansen, Keith A; DeWitt, Jason

2005-12-01

To describe an unusual, premenarchal presentation of an obstructive vaginal anomaly. Case Report. University Medical Center. Premenarchal subject Vaginogram, vaginal septum resection. Vaginal septum resection with resolution of vaginal discharge. This case demonstrates some of the typical features of uterus didelphys bicollis with incomplete obstructing hemivagina, but had a unique presentation with premenarchal, recurrent vaginal discharge. Typically, patients with an obstructing mullerian anomaly present after menarche with pelvic pain and a mass. The vaginogram assists in the preoperative definition of abnormal anatomy which allows the surgeon to develop the most appropriate surgical approach. Resection of this incompletely obstructing vaginal septum resulted in resolution of the recurrent vaginal discharge.

Hysterectomy - vaginal - discharge

MedlinePlus

Vaginal hysterectomy - discharge; Laparoscopically assisted vaginal hysterectomy - discharge; LAVH - discharge ... you were in the hospital, you had a vaginal hysterectomy. Your surgeon made a cut in your ...

Vaginal foreign bodies.

PubMed

Stricker, T; Navratil, F; Sennhauser, F H

2004-04-01

To evaluate the clinical features and outcome in girls with a vaginal foreign body. Retrospective review of medical records of 35 girls with a vaginal foreign body seen in an outpatient clinic for paediatric and adolescent gynaecology between 1980 and 2000. The ages ranged from 2.6 to 9.2 years. The most common symptom was blood-stained vaginal discharge/vaginal bleeding (49%). Duration of symptoms varied from 1 day to 2 years. Fifty-four percent of the patients recalled insertion of the foreign object, usually by the girl herself. All but three patients (91%) either recalled insertion of the foreign object and/or had vaginal bleeding or blood-stained or foul-smelling vaginal discharge, and/or visualization or palpation of the foreign body in physical examination. Symptoms resolved after removal of the foreign body followed by a single irrigation with Providon-Iod (Betadine). In the majority of patients a carefully obtained history and physical examination suggest the diagnosis of a vaginal foreign object. The leading symptoms are vaginal bleeding and blood-stained or foul smelling vaginal discharge. Removal of the foreign object followed by a single irrigation with Providon-Iod is the definitive treatment and does not require additional measures.

Clinical characteristics of aerobic vaginitis and its association to vaginal candidiasis, trichomonas vaginitis and bacterial vaginosis.

PubMed

Jahic, Mahira; Mulavdic, Mirsada; Nurkic, Jasmina; Jahic, Elmir; Nurkic, Midhat

2013-12-01

Examine clinical characteristics of aerobic vaginitis and mixed infection for the purpose of better diagnostic accuracy and treatment efficiency. Prospective research has been conducted at Clinic for Gynecology and Obstetrics, Department for Microbiology and Pathology at Polyclinic for laboratory diagnostic and Gynecology and Obstetrics Department at Health Center Sapna. Examination included 100 examinees with the signs of vaginitis. anamnesis, clinical, gynecological and microbiological examination of vaginal smear. The average age of the examinees was 32,62±2,6. Examining vaginal smears of the examinees with signs of vaginitis in 96% (N-96) different microorganisms have been isolated, while in 4% (N-4) findings were normal. AV has been found in 51% (N-51) of the examinees, Candida albicans in 17% (N-17), BV in 15% (N-15), Trichomonas vaginalis in 13% (N-13). In 21% (N-21) AV was diagnosed alone while associated with other agents in 30% (N-30). Most common causes of AV are E. coli (N-55) and E. faecalis (N-52). AV and Candida albicanis have been found in (13/30, 43%), Trichomonas vaginalis in (9/30, 30%) and BV (8/30, 26%). Vaginal secretion is in 70,05% (N-36) yellow coloured, red vagina wall is recorded in 31,13% (N-16) and pruritus in 72,54% (N-37). Increased pH value of vagina found in 94,10% (N-48). The average pH value of vaginal environment was 5,15±0,54 and in associated presence of AV and VVC, TV and BV was 5,29±0,56 which is higher value considering presence of AV alone but that is not statistically significant difference (p>0,05). Amino-odor test was positive in 29,94% (N-15) of associated infections. Lactobacilli are absent, while leukocytes are increased in 100% (N-51) of the examinees with AV. AV is vaginal infection similar to other vaginal infections. It is important to be careful while diagnosing because the treatment of AV differentiates from treatment of other vaginitis.

FECAL PROGESTERONE METABOLITES IN POSTPARTUM SIBERIAN FLYING SQUIRRELS.

PubMed

Shimamoto, Tatsuki; Suzuki, Kei K; Hamada, Mizuho; Furukawa, Ryuji; Matsui, Motozumi; Yanagawa, Hisashi

2018-03-01

The Siberian flying squirrel ( Pteromys volans) produces up to two litters a year. To deliver second litters in breeding season, P. volans may have a postpartum estrus similarly to that of a variety of small mammals. If this were the case, females would have periods of elevated progesterone levels because of the formation of corpora lutea (CL) after postpartum ovulation. To test this hypothesis, fecal progesterone metabolite dynamics was investigated during lactation in this species using an enzyme immunoassay. In five of the six lactating females, periods of high fecal progesterone metabolite concentration were observed, and, furthermore, progesterone secretion patterns were periodic. Therefore, the source of progesterone during lactation could be arising CL from postpartum ovulation, indicating that ovarian activity was reinitiated after parturition and the CL that formed began secreting progesterone. This study thus showed that P. volans likely has the physiologic potential to mate during lactation.

Value of bacterial culture of vaginal swabs in diagnosis of vaginal infections.

PubMed

Nenadić, Dane; Pavlović, Miloš D

2015-06-01

Vaginal and cervical swab culture is still very common procedure in our country's everyday practice whereas simple and rapid diagnostic methods have been very rarely used. The aim of this study was to show that the employment of simple and rapid diagnostic tools [vaginal fluid wet mount microscopy (VFWMM), vaginal pH and potassium hydroxide (KOH) test] offers better assessment of vaginal environment than standard microbiologic culture commonly used in Serbia. This prospective study included 505 asymptomatic pregnant women undergoing VFWMM, test with 10% KOH, determination of vaginal pH and standard culture of cervicovaginal swabs. Combining findings from the procedures was used to make diagnoses of bacterial vaginosis (BV) and vaginitis. In addition, the number of polymorphonuclear leukocytes (PMN) was determined in each sample and analyzed along with other findings. Infections with Candida albicans and Trichomonas vaginalis were confirmed or excluded by microscopic examination. In 36 (6%) patients cervicovaginal swab cultures retrieved several aerobes and facultative anaerobes, whereas in 52 (11%) women Candida albicans was isolated. Based on VFWMM findings and clinical criteria 96 (19%) women had BV, 19 (4%) vaginitis, and 72 (14%) candidiasis. Of 115 women with BV and vaginitis, pH 4.5 was found in 5, and of 390 with normal findings 83 (21%) had vaginal pH 4.5. Elevated numbers of PMN were found in 154 (30%) women--in 83 (54%) of them VFWMM was normal. Specificity and sensitivity of KOH test and vaginal pH determination in defining pathological vaginal flora were 95% and 81%, and 79% and 91%, respectively. Cervicovaginal swab culture is expensive but almost non-informative test in clinical practice. The use of simpler and rapid methods as vaginal fluid wet mount microscopy, KOH test and vaginal pH offers better results in diagnosis, and probably in the treatment and prevention of sequels of vaginal infections.

Sensitive Tenofovir Resistance Screening of HIV-1 From the Genital and Blood Compartments of Women With Breakthrough Infections in the CAPRISA 004 Tenofovir Gel Trial

PubMed Central

Wei, Xierong; Hunt, Gillian; Abdool Karim, Salim S.; Naranbhai, Vivek; Sibeko, Sengeziwe; Abdool Karim, Quarraisha; Li, Jin-fen; Kashuba, Angela D. M.; Werner, Lise; Passmore, Jo-Ann S.; Morris, Lynn; Heneine, Walid; Johnson, Jeffrey A.

2014-01-01

The Centre for the AIDS Programme of Research in South Africa 004 (CAPRISA 004) study demonstrated that vaginally applied tenofovir gel is a promising intervention for protecting women from sexually acquiring human immunodeficiency virus (HIV). However, the potential for emergence of tenofovir resistance remains a concern in women who seroconvert while using the gel despite the lack of plasma virus resistance as assessed by population sequencing during the trial. We applied highly sensitive polymerase chain reaction–based assays to screen for tenofovir resistance in plasma and vaginal swab specimens. The absence of mutation detection suggested little immediate risk of tenofovir-resistant HIV-1 emergence and forward transmission in settings in which gel users are closely monitored for HIV seroconversion. PMID:24436453

Vaginal contraceptive film gains wider acceptance.

PubMed

1992-09-01

In US health departments and family planning clinics, women are beginning to accept vaginal contraceptive film more widely. Further, direct sales of this method, which is also distributed over the counter, has increased. In fact, in 1991, vaginal contraceptive film was the top selling contraceptive in pharmacies. This 2.5 sq. inch water-soluble film is impregnated with nonoxynol-9. The woman uses her finger to insert the folded square as close as possible to the cervix 5-60 minutes before intercourse. If the time between acts of intercourse is greater than 1 hour, she must insert another square. After it dissolves, it is a firm gel removed by vaginal and cervical fluids. The company realizes that its relatively high cost (about $3.59 for 3 films) prevents some family planning providers from offering the film. It has tried to cut costs by not using extra packaging material and by manufacturing it in the US instead of ain England. A manager of the family planning clinic at R.E. Thomason County Hospital in El Paso, Texas, notes that user compliance is higher with the vaginal contraceptive film than foam. In fact, patients at the Planned Parenthood League of Middlesex County, New Jersey, favor the film because it is less messy than foam. Teenagers in El Paso prefer the film because of the privacy issue and gives them more control to protect themselves from pregnancy. A worker at the New Jersey clinic recommends the film as a backup method for women beginning to use oral contraceptives. She also suggests to patients requesting condoms to also use the film. The company makes the same recommendation. Yet, family planning workers note that some women cannot convince partners to use the condom. 90% of patients at the El Paso clinic are Hispanic, and they tend to not accept condom use. Some providers suggest using 2 applications of the film to defend against sexually transmitted diseases, but there is no evidence that double application actually does so.

Alternative splicing and the progesterone receptor in breast cancer

PubMed Central

Cork, David MW; Lennard, Thomas WJ; Tyson-Capper, Alison J

2008-01-01

Progesterone receptor status is a marker for hormone responsiveness and disease prognosis in breast cancer. Progesterone receptor negative tumours have generally been shown to have a poorer prognosis than progesterone receptor positive tumours. The observed loss of progesterone receptor could be through a range of mechanisms, including the generation of alternatively spliced progesterone receptor variants that are not detectable by current screening methods. Many progesterone receptor mRNA variants have been described with deletions of various whole, multiple or partial exons that encode differing protein functional domains. These variants may alter the progestin responsiveness of a tissue and contribute to the abnormal growth associated with breast cancer. Absence of specific functional domains from these spliced variants may also make them undetectable or indistinguishable from full length progesterone receptor by conventional antibodies. A comprehensive investigation into the expression profile and activity of progesterone receptor spliced variants in breast cancer is required to advance our understanding of tumour hormone receptor status. This, in turn, may aid the development of new biomarkers of disease prognosis and improve adjuvant treatment decisions. PMID:18557990

Progesterone action in breast, uterine, and ovarian cancers

PubMed Central

Diep, Caroline H.; Daniel, Andrea R.; Mauro, Laura J.; Knutson, Todd P.; Lange, Carol A.

2015-01-01

Progesterone and progesterone receptors (PR) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the uterus and protects the ovary from neoplastic transformation. Progesterone-dependent actions and associated biology in diverse tissues and tumors are mediated by two progesterone receptor isoforms, PR-A and PR-B. These isoforms are subject to altered transcriptional activity or expression levels, differential cross-talk with growth factor signaling pathways, and distinct post-translational modifications and cofactor binding partners. Herein, we summarize and discuss the recent literature focused on progesterone and PR isoform-specific actions in breast, uterine, and ovarian cancers. Understanding the complexity of context-dependent PR actions in these tissues is critical to developing new models that will allow us to advance our knowledge base with the goal of revealing novel and efficacious therapeutic regimens for these hormone-responsive diseases. PMID:25587053

Progesterone Receptors: Form and Function in Brain

PubMed Central

Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

2008-01-01

Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging. PMID:18374402

Overview of progesterone profiles in dairy cows.

PubMed

Blavy, P; Derks, M; Martin, O; Höglund, J K; Friggens, N C

2016-09-01

The aim of this study was to gain a better understanding of the variability in shape and features of all progesterone profiles during estrus cycles in cows and to create templates for cycle shapes and features as a base for further research. Milk progesterone data from 1418 estrus cycles, coming from 1009 lactations, was obtained from the Danish Cattle Research Centre in Foulum, Denmark. Milk samples were analyzed daily using a Ridgeway ELISA-kit. Estrus cycles with less than 10 data points or shorter than 4 days were discarded, after which 1006 cycles remained in the analysis. A median kernel of three data points was used to smooth the progesterone time series. The time between start of progesterone rise and end of progesterone decline was identified by fitting a simple model consisting of base length and a quadratic curve to progesterone data, and this luteal-like phase (LLP) was used for further analysis. The data set of 1006 LLP's was divided into five quantiles based on length. Within quantiles, a cluster analysis was performed on the basis of shape distance. Height, upward and downward slope, and progesterone level on Day 5 were compared between quantiles. Also, the ratio of typical versus atypical shapes was described, using a reference curve on the basis of data in Q1-Q4. The main results of this article were that (1) most of the progesterone profiles showed a typical profile, including the ones that exceeded the optimum cycle length of 24 days; (2) cycles in Q2 and Q3 had steeper slopes and higher peak progesterone levels than cycles in Q1 and Q4 but, when normalized, had a similar shape. Results were used to define differences between quantiles that can be used as templates. Compared to Q1, LLP's in Q2 had a shape that is 1.068 times steeper and 1.048 times higher. Luteal-like phases in Q3 were 1.053 times steeper and 1.018 times higher. Luteal-like phases in Q4 were 0.977 times steeper and 0.973 times higher than LLP's in Q1. This article adds to our

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP

Vaginal yeast infection

MedlinePlus

Yeast infection - vagina; Vaginal candidiasis; Monilial vaginitis ... Most women have a vaginal yeast infection at some time. Candida albicans is a common type of fungus. It is often found in small amounts in the ...

A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

PubMed Central

Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W.; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M.

2014-01-01

Abstract Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be “very likely” to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug. PMID:24070431

A randomized male tolerance study of dapivirine gel following multiple topical penile exposures (MTN 012/IPM 010).

PubMed

Cranston, Ross D; Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M

2014-02-01

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be "very likely" to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug.

Endocrine correlates of reproduction in the wolf. I. Serum progesterone, estradiol and LH during the estrous cycle

USGS Publications Warehouse

Seal, U.S.; Plotka, E.D.; Packard, J.M.; Mech, L.D.

1979-01-01

The estrous cycle of 10 intact female wolves, aged 8 months-8 years at the initiation of the study, was characterized in terms of vaginal smears, behavioral observations and serum concentrations of estradiol-17β, progesterone and luteinizing hormone (LH) from January through June. No estrous cycles occurred in these animals between June and December. All were housed with male wolves. Two pups and 1 adult remained anestrous during this interval. One pup and 2 adults produced litters between May 4-6. Four adults exhibited endocrine changes similar to those of the pregnant animals but no litters or signs of abortion were observed. The duration of proestrus was 15.7 ± 1.6 days (X ± SEM, n = 6), of estrus 9.0 ± 1.2 days (n = 4) and of the luteal phase 63 ± 2 days (n = 6). The duration of pregnancy was between 60-65 days. The anestrous females (86 blood samples) had 6 progesterone values between 1-2 ng/ml and the remainder below 1 ng/ml. Their estradiol-17β concentrations varied between 5-20 pg/ml. Values for LH varied between 0.1-2 ng/ml, except for 1 value above 15 ng/ml for each of the 2 anestrous pups on 12 January.The 7 estrous animals (260 samples) included 1 pup and 2 adults that delivered litters. Estradiol-17β varied between 10-20 pg/ml during proestrus, peaked at 30-70 pg/ml late in proestrus and fluctuated between 10-30 pg/ml during pregnancy or the duration of luteal activity in the nonpregnant animals. The preovulatory LH rise, 5-15 ng/ml, extended over 3 days during and immediately following the peak estradiol-17β values. An earlier elevation in LH was observed in 3 of the estrous animals. Progesterone began increasing during the LH surge and peaked 11-14 days later at 22-40 ng/ml. Progesterone concentrations greater than 3 ng/ml were maintained for 56-68 days in 6 of the 7 animals exhibiting estrus. Progesterone concentrations declined at parturition but continued to fluctuate between 0.2-3 ng/ml for 3-6 weeks.

Clinical Characteristics of Aerobic Vaginitis and Its Association to Vaginal Candidiasis, Trichomonas Vaginitis and Bacterial Vaginosis

PubMed Central

Jahic, Mahira; Mulavdic, Mirsada; Nurkic, Jasmina; Jahic, Elmir; Nurkic, Midhat

2013-01-01

ABSTRACT Aim of the work: Examine clinical characteristics of aerobic vaginitis and mixed infection for the purpose of better diagnostic accuracy and treatment efficiency. Materials and methods: Prospective research has been conducted at Clinic for Gynecology and Obstetrics, Department for Microbiology and Pathology at Polyclinic for laboratory diagnostic and Gynecology and Obstetrics Department at Health Center Sapna. Examination included 100 examinees with the signs of vaginitis. Examination consisted of: anamnesis, clinical, gynecological and microbiological examination of vaginal smear. Results: The average age of the examinees was 32,62±2,6. Examining vaginal smears of the examinees with signs of vaginitis in 96% (N-96) different microorganisms have been isolated, while in 4% (N-4) findings were normal. AV has been found in 51% (N-51) of the examinees, Candida albicans in 17% (N-17), BV in 15% (N-15), Trichomonas vaginalis in 13% (N-13). In 21% (N-21) AV was diagnosed alone while associated with other agents in 30% (N-30). Most common causes of AV are E. coli (N-55) and E. faecalis (N-52). AV and Candida albicanis have been found in (13/30, 43%), Trichomonas vaginalis in (9/30, 30%) and BV (8/30, 26%). Vaginal secretion is in 70,05% (N-36) yellow coloured, red vagina wall is recorded in 31,13% (N-16) and pruritus in 72,54% (N-37). Increased pH value of vagina found in 94,10% (N-48). The average pH value of vaginal environment was 5,15±0,54 and in associated presence of AV and VVC, TV and BV was 5,29±0,56 which is higher value considering presence of AV alone but that is not statistically significant difference (p>0,05). Amino-odor test was positive in 29,94% (N-15) of associated infections. Lactobacilli are absent, while leukocytes are increased in 100% (N-51) of the examinees with AV. Conclusion: AV is vaginal infection similar to other vaginal infections. It is important to be careful while diagnosing because the treatment of AV differentiates from

Optimal routes of administration, vehicles and timing of progesterone treatment for inhibition of delivery during pregnancy.

PubMed

Fang, Dajun; Moreno, Mario; Garfield, Robert E; Kuon, Ruben; Xia, Huimin

2017-09-01

Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone. Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve ® (also known as Crinone ® ), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied. Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P<0.05-<0.001) delay delivery, but vaginal Prochieve ® did not. Administration of P4 in late gestation also prevented (P<0.001) delivery even when given 8h before delivery. Prochieve ® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration. Copyright © 2017. Published by Elsevier B.V.

Local oestrogen for vaginal atrophy in postmenopausal women.

PubMed

Suckling, J; Lethaby, A; Kennedy, R

2003-01-01

differences favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and six looked at adverse effects. One trial showed significant adverse effects of cream (conjugated equine oestrogen) when compared to tablets (estradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by progestagen challenge test in the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (estradiol). Nine studies compared acceptability to the participants by comparing comfort of product, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the estradiol releasing vaginal ring. Creams, pessaries, tablets and the estradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects noted following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the estradiol releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Local oestrogen for vaginal atrophy in postmenopausal women.

PubMed

Suckling, J; Lethaby, A; Kennedy, R

2006-10-18

symptoms of vaginal atrophy, results indicated significant findings favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and seven looked at adverse effects. One trial showed significant adverse effects of the cream (conjugated equine oestrogen) when compared to tablets (oestradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by a progestagen challenge test with the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to the cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (oestradiol). Eleven studies compared acceptability to the participants by comparing: comfort of product use, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the oestradiol-releasing vaginal ring. Creams, pessaries, tablets and the oestradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following use of the cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the oestradiol-releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Effects of progesterone and its metabolites on human granulosa cells.

PubMed

Pietrowski, D; Gong, Y; Mairhofer, M; Gessele, R; Sator, M

2014-02-01

The corpus luteum (CL) is under control of gonadotrophic hormones and produces progesterone, which is necessary for endometrial receptivity. Recent studies have shown that progesterone and its metabolites are involved in cell proliferation and apoptosis of cancer cells. Here weanalyzed the role of progesterone and its meta-bolites on luteinized granulosa cells (LGC) by FACS analysis and quantitative Real-Time PCR. We detected the mRNA of the progesterone metabolizing genes SRD5A1, AKR1C1, and AKR1C2 in LGC. The stimulation of LGC with progesterone or progesterone metabolites did not show any effect on the mRNA expression of these genes. However, a downregulation of Fas expression was found to be accomplished by progesterone and human chorionic gonadotropin. Our findings do not support the concept of an effect of progesterone metabolites on LGCs. However, it suggests an antiapoptotic effect of hCG and progesterone during corpus luteum development by downregulation of Fas. © Georg Thieme Verlag KG Stuttgart · New York.

Yeast Infection (Vaginal)

MedlinePlus

Yeast infection (vaginal) Overview A vaginal yeast infection is a fungal infection that causes irritation, discharge and intense itchiness ... symptoms Causes The fungus candida causes a vaginal yeast infection. Your vagina naturally contains a balanced mix of yeast, including ...

Protection against rat vaginal candidiasis by adoptive transfer of vaginal B lymphocytes.

PubMed

De Bernardis, Flavia; Santoni, Giorgio; Boccanera, Maria; Lucciarini, Roberta; Arancia, Silvia; Sandini, Silvia; Amantini, Consuelo; Cassone, Antonio

2010-06-01

Vulvovaginal candidiasis is a mucosal infection affecting many women, but the immune mechanisms operating against Candida albicans at the mucosal level remain unknown. A rat model was employed to further characterize the contribution of B and T cells to anti-Candida vaginal protection. Particularly, the protective role of vaginal B cells was studied by means of adoptive transfer of vaginal CD3(-) CD5(+) IgM(+) cells from Candida-immunized rats to naïve animals. This passive transfer of B cells resulted into a number of vaginal C. albicans CFU approximately 50% lower than their controls. Sorted CD3(-) CD5(+) IgM(+) vaginal B lymphocytes from Candida-infected rats proliferated in response to stimulation with an immunodominant mannoprotein (MP) antigen of the fungus. Importantly, anti-MP antibodies and antibody-secreting B cells were detected in the supernatant and cell cultures, respectively, of vaginal B lymphocytes from infected rats incubated in vitro with vaginal T cells and stimulated with MP. No such specific antibodies were found when using vaginal B cells from uninfected rats. Furthermore, inflammatory and anti-inflammatory cytokines, such as interleukin-2 (IL-2), IL-6 and IL-10, were found in the supernatant of vaginal B cells from infected rats. These data are evidence of a partial anti-Candida protective role of CD3(-) CD5(+) IgM(+) vaginal B lymphocytes in our experimental model.

Vaginal Microbiota.

PubMed

Mendling, Werner

2016-01-01

The knowledge about the normal and abnormal vaginal microbiome has changed over the last years. Culturing techniques are not suitable any more for determination of a normal or abnormal vaginal microbiota. Non culture-based modern technologies revealed a complex and dynamic system mainly dominated by lactobacilli.The normal and the abnormal vaginal microbiota are complex ecosystems of more than 200 bacterial species influenced by genes, ethnic background and environmental and behavioral factors. Several species of lactobacilli per individuum dominate the healthy vagina. They support a defense system together with antibacterial substances, cytokines, defensins and others against dysbiosis, infections and care for an normal pregnancy without preterm birth.The numbers of Lactobacillus (L.) iners increase in the case of dysbiosis.Bacterial vaginosis (BV) - associated bacteria (BVAB), Atopobium vaginae and Clostridiales and one or two of four Gardnerella vaginalis - strains develop in different mixtures and numbers polymicrobial biofilms on the vaginal epithelium, which are not dissolved by antibiotic therapies according to guidelines and, thus, provoke recurrences.Aerobic vaginitis seems to be an immunological disorder of the vagina with influence on the microbiota, which is here dominated by aerobic bacteria (Streptococcus agalactiae, Escherichia coli). Their role in AV is unknown.Vaginal or oral application of lactobacilli is obviously able to improve therapeutic results of BV and dysbiosis.

Progesterone Is Essential for Protecting against LPS-Induced Pregnancy Loss. LIF as a Potential Mediator of the Anti-inflammatory Effect of Progesterone

PubMed Central

Aisemberg, Julieta; Vercelli, Claudia A.; Bariani, María V.; Billi, Silvia C.; Wolfson, Manuel L.; Franchi, Ana M.

2013-01-01

Lipopolysaccharide (LPS) administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF), which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders. PMID:23409146

Thermoreversible gel formulation containing sodium lauryl sulfate as a potential contraceptive device.

PubMed

Haineault, Caroline; Gourde, Pierrette; Perron, Sylvie; Désormeaux, André; Piret, Jocelyne; Omar, Rabeea F; Tremblay, Roland R; Bergeron, Michel G

2003-08-01

The contraceptive properties of a gel formulation containing sodium lauryl sulfate were investigated in both in vitro and in vivo models. Results showed that sodium lauryl sulfate inhibited, in a concentration-dependent manner, the activity of sheep testicular hyaluronidase. Sodium lauryl sulfate also completely inhibited human sperm motility as evaluated by the 30-sec Sander-Cramer test. The acid-buffering capacity of gel formulations containing sodium lauryl sulfate increased with the molarity of the citrate buffers used for their preparations. Furthermore, experiments in which semen was mixed with undiluted gel formulations in different proportions confirmed their physiologically relevant buffering capacity. Intravaginal application of the gel formulation containing sodium lauryl sulfate to rabbits before their artificial insemination with freshly ejaculated semen completely prevented egg fertilization. The gel formulation containing sodium lauryl sulfate was fully compatible with nonlubricated latex condoms. Taken together, these results suggest that the gel formulation containing sodium lauryl sulfate could represent a potential candidate for use as a topical vaginal spermicidal formulation to provide fertility control in women.

Progesterone Treatment in Two Rat Models of Ocular Ischemia

PubMed Central

Allen, Rachael S.; Olsen, Timothy W.; Sayeed, Iqbal; Cale, Heather A.; Morrison, Katherine C.; Oumarbaeva, Yuliya; Lucaciu, Irina; Boatright, Jeffrey H.; Pardue, Machelle T.; Stein, Donald G.

2015-01-01

Purpose. To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models. Methods. Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. Results. Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. Conclusions. Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone. PMID:26024074

Twice-daily application of HIV microbicides alter the vaginal microbiota.

PubMed

Ravel, Jacques; Gajer, Pawel; Fu, Li; Mauck, Christine K; Koenig, Sara S K; Sakamoto, Joyce; Motsinger-Reif, Alison A; Doncel, Gustavo F; Zeichner, Steven L

2012-12-18

Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 study of twice-daily application over 13.5 days of 1 of 3 gel products: a hydroxyethylcellulose (HEC)-based "universal" placebo (10 subjects), 6% cellulose sulfate (CS; 13 subjects), and 4% nonoxynol-9 (N-9; 12 subjects). We used mixed effects models inferred using Bayesian Markov chain Monte Carlo methods, which showed that treatment with active agents shifted the microbiota toward a community type lacking significant numbers of Lactobacillus spp. and dominated by strict anaerobes. This state of the vaginal microbiota was associated with a low or intermediate Nugent score and was not identical to bacterial vaginosis, an HIV transmission risk factor. The placebo arm contained a higher proportion of communities dominated by Lactobacillus spp., particularly L. crispatus, throughout treatment. The data suggest that molecular evaluation of microbicide effects on vaginal microbiota may be a critical endpoint that should be incorporated in early clinical assessment of microbicide candidates. Despite large prevention efforts, HIV transmission and acquisition rates remain unacceptably high. In developing countries, transmission mainly occurs through heterosexual intercourse, where women are significantly more vulnerable to infection than men. Vaginal microbicides are considered to

Vaginal Cancer—Patient Version

Cancer.gov

Two-thirds of vaginal cancer cases are caused by human papillomavirus (HPV). Vaccines that protect against infection with HPV may reduce the risk of vaginal cancer. When found early, vaginal cancer can often be cured. Start here to find information on vaginal cancer treatment and research.

More frequent vaginal orgasm is associated with experiencing greater excitement from deep vaginal stimulation.

PubMed

Brody, Stuart; Klapilova, Katerina; Krejčová, Lucie

2013-07-01

Research indicated that: (i) vaginal orgasm (induced by penile-vaginal intercourse [PVI] without concurrent clitoral masturbation) consistency (vaginal orgasm consistency [VOC]; percentage of PVI occasions resulting in vaginal orgasm) is associated with mental attention to vaginal sensations during PVI, preference for a longer penis, and indices of psychological and physiological functioning, and (ii) clitoral, distal vaginal, and deep vaginal/cervical stimulation project via different peripheral nerves to different brain regions. The aim of this study is to examine the association of VOC with: (i) sexual arousability perceived from deep vaginal stimulation (compared with middle and shallow vaginal stimulation and clitoral stimulation), and (ii) whether vaginal stimulation was present during the woman's first masturbation. A sample of 75 Czech women (aged 18-36), provided details of recent VOC, site of genital stimulation during first masturbation, and their recent sexual arousability from the four genital sites. The association of VOC with: (i) sexual arousability perceived from the four genital sites and (ii) involvement of vaginal stimulation in first-ever masturbation. VOC was associated with greater sexual arousability from deep vaginal stimulation but not with sexual arousability from other genital sites. VOC was also associated with women's first masturbation incorporating (or being exclusively) vaginal stimulation. The findings suggest (i) stimulating the vagina during early life masturbation might indicate individual readiness for developing greater vaginal responsiveness, leading to adult greater VOC, and (ii) current sensitivity of deep vaginal and cervical regions is associated with VOC, which might be due to some combination of different neurophysiological projections of the deep regions and their greater responsiveness to penile stimulation. © 2013 International Society for Sexual Medicine.

Management of aerobic vaginitis.

PubMed

Tempera, Gianna; Furneri, Pio Maria

2010-01-01

Aerobic vaginitis is a new nonclassifiable pathology that is neither specific vaginitis nor bacterial vaginosis. The diversity of this microbiological peculiarity could also explain several therapeutic failures when patients were treated for infections identified as bacterial vaginosis. The diagnosis 'aerobic vaginitis' is essentially based on microscopic examinations using a phase-contrast microscope (at ×400 magnification). The therapeutic choice for 'aerobic vaginitis' should take into consideration an antibiotic characterized by an intrinsic activity against the majority of bacteria of fecal origin, bactericidal effect and poor/absent interference with the vaginal microbiota. Regarding the therapy for aerobic vaginitis when antimicrobial agents are prescribed, not only the antimicrobial spectrum but also the presumed ecological disturbance on the anaerobic and aerobic vaginal and rectal microbiota should be taken into a consideration. Because of their very low impact on the vaginal microbiota, kanamycin or quinolones are to be considered a good choice for therapy. Copyright © 2010 S. Karger AG, Basel.

Vaginal Bleeding

MedlinePlus

... bleeding is any vaginal bleeding unrelated to normal menstruation. This type of bleeding may include spotting of ... two or more hours. Normal vaginal bleeding, or menstruation, occurs every 21 to 35 days when the ...

Vaginal Odor

MedlinePlus

... usually don't cause vaginal odors. Neither do yeast infections. Generally, if you have vaginal odor without ... Avoid douching. All healthy vaginas contain bacteria and yeast. The normal acidity of your vagina keeps bacteria ...

Clindamycin Vaginal

MedlinePlus

... an infection caused by an overgrowth of harmful bacteria in the vagina). Clindamycin is in a class ... works by slowing or stopping the growth of bacteria. Vaginal clindamycin cannot be used to treat vaginal ...

Vaginal Diseases

MedlinePlus

Vaginal problems are some of the most common reasons women go to the doctor. They may have ... common problem is vaginitis, an inflammation of the vagina. Other problems that affect the vagina include sexually ...

delta 9-(16 alpha-/sup 125/I)iodo-19-nortestosterone: a gamma-emitting photoaffinity label for the progesterone receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, D.J.; Bullock, D.W.; Hoyte, R.M.

1988-05-01

We have synthesized 16 alpha-iodo-4,9-estradien-17 beta-ol-3-one (delta 9-16 alpha-iodo-19-nortestosterone (delta 9-INT)) labeled with 125I (delta 9-(16 alpha-125I)INT) to provide a new gamma-emitting photoaffinity ligand for the progesterone receptor that has many advantages over the currently available (3H)R5020. We have characterized the interaction of delta 9-(16 alpha-125I)INT with the rabbit uterine progesterone receptor and have demonstrated the usefulness of this compound for studies of receptor structure. The binding of 2 nM (3H)progesterone to receptor in rabbit uterine cytosol was specifically competed for by 19-nortestosterone, 16 alpha-iodo-19-nortestosterone, and delta 9-INT. Scatchard analysis demonstrated that delta 9-(16 alpha-125I)INT and (3H)progesterone estimated the samemore » number of binding sites in rabbit uterine cytosol, with a Kd for delta 9-(16 alpha-125I)INT of about 2.7 nM. The binding of delta 9-(16 alpha-125I)INT was inhibited by both progesterone and R5020, whereas testosterone, estradiol, and 5 alpha-dihydrotestosterone were ineffective. In cytosol, delta 9-(16 alpha-125I)INT covalently labeled the same mol wt receptor forms as (3H)R5020. Although the efficiency of cross-linking was similar for (3H)R5020 (3%) and delta 9-(16 alpha-125I)INT (4%), the radioactivity was 10-fold greater due to the higher specific activity of delta 9-(16 alpha-125I)INT and the lack of sample quench. The use of delta 9-(16 alpha-125I)INT greatly increases the sensitivity and efficiency of the photoaffinity labeling technique; it will provide a valuable tool for further studies of the progesterone receptor, allowing the detection of receptor in dilute cytosol after gel electrophoresis under denaturing conditions.« less

Successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia: A rare case report.

PubMed

Liu, Yu; Wang, Yi-Feng

2017-07-01

We report a case of successful vaginal delivery after vaginal reconstruction with labium minus flaps in a 23-year-old patient with congenital vaginal atresia. The patient primarily presented with amenorrhea and cyclic abdominal pain; transabdominal ultrasonography revealed an enlarged uterus due to hematometra and absence of the lower segment of the vagina. Eight years ago, she had undergone an unsuccessful attempt at canalization at a local hospital. Upon referral to our hospital, she underwent vaginal reconstruction with labium minus flaps. Four months after this procedure, she became pregnant and, subsequently, successfully and safely vaginally delivered a healthy female baby weighing 3250 g at 38 +1 weeks' gestation. The delivery did not involve perineal laceration by lateral episiotomy. To the best of our knowledge, this is the first reported case of successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia. © 2017 Japan Society of Obstetrics and Gynecology.

Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

PubMed Central

Kim, J. Julie; Kurita, Takeshi

2013-01-01

Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis.

PubMed

Donders, Gilbert G G; Vereecken, Annie; Bosmans, Eugene; Dekeersmaecker, Alfons; Salembier, Geert; Spitz, Bernard

2002-01-01

To define an entity of abnormal vaginal flora: aerobic vaginitis. Observational study. University Hospital Gasthuisberg, Leuven, Belgium. 631 women attending for routine prenatal care or attending vaginitis clinic. Samples were taken for fresh wet mount microscopy of vaginal fluid, vaginal cultures and measurement of lactate, succinate and cytokine levels in vaginal fluid. Smears deficient in lactobacilli and positive for clue cells were considered to indicate a diagnosis of bacterial vaginosis. Aerobic vaginitis was diagnosed if smears were deficient in lactobacilli, positive for cocci or coarse bacilli, positive for parabasal epithelial cells, and/or positive for vaginal leucocytes (plus their granular aspect). Genital complaints include red inflammation, yellow discharge, vaginal dyspareunia. Group B streptococci, escherichia coli, staphylococcus aureus and trichomonas vaginalis are frequently cultured. Vaginal lactate concentration is severely depressed in women with aerobic vaginitis, as in bacterial vaginosis, but vaginal succinate is not produced. Also in contrast to bacterial vaginosis, aerobic vaginitis produces a host immune response that leads to high production of interleukin-6, interleukin-1-beta and leukaemia inhibitory factor in the vaginal fluid. Aerobic vaginitis is associated with aerobic micro-organisms, mainly group B streptococci and E. coli. Its characteristics are different from those of bacterial vaginosis and elicit an important host response. The most severe form of aerobic vaginitis equals desquamative inflammatory vaginitis. In theory, aerobic vaginitis may be a better candidate than bacterial vaginosis as the cause of pregnancy complications, such as ascending chorioamnionitis, preterm rupture of the membranes and preterm delivery.

Progesterone-induced Neuroprotection: Factors that may predict therapeutic efficacy

PubMed Central

Singh, Meharvan; Su, Chang

2013-01-01

Both progesterone and estradiol have well-described neuroprotective effects against numerous insults in a variety of cell culture models, animal models and in humans. However, the efficacy of these hormones may depend on a variety of factors, including the type of hormone used (ex. progesterone versus medroxyprogesterone acetate), the duration of the postmenopausal period prior to initiating the hormone intervention, and potentially, the age of the subject. The latter two factors relate to the proposed existence of a “window of therapeutic opportunity” for steroid hormones in the brain. While such a window of opportunity has been described for estrogen, there is a paucity of information to address whether such a window of opportunity exists for progesterone and its related progestins. Here, we review known cellular mechanisms likely to underlie the protective effects of progesterone and furthermore, describe key differences in the neurobiology of progesterone and the synthetic progestin, medroxyprogesterone acetate (MPA). Based on the latter, we offer a model that defines some of the key cellular and molecular players that predict the neuroprotective efficacy of progesterone. Accordingly, we suggest how changes in the expression or function of these cellular and molecular targets of progesterone with age or prolonged duration of hormone withdrawal (such as following surgical or natural menopause) may impact the efficacy of progesterone. PMID:23340161

Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells.

PubMed

Li, Mingwei; Sun, Jianxia; Zou, Feiyan; Bai, Shun; Jiang, Xinwei; Jiao, Rui; Ou, Shiyi; Zhang, Hui; Su, Zhijian; Huang, Yadong; Bai, Weibin

2017-10-01

The food contaminant acrylamide (AA) is usually recognized as a probable human carcinogen. In addition, AA has also been found able to induce male infertility in animals. Interestingly, resent research work revealed that the toxic effect of AA on the ability of male reproduction in vivo may due to glycidamide (GA) which is the metabolite of AA. In this study, R2C Leydig cells was used to investigate the toxic effects of GA on progesterone production. GA caused dose-dependent inhibition on the cell growth, with IC 25 , IC 50, and IC 75 values found at 0.635, 0.872, and 1.198 mM, respectively. The results of single cell gel/Comet assay showed that GA significantly induced early-phase cell apoptosis, reduced progesterone production, as well as decreasing the protein expression of steroidogenic acute regulatory (StAR) in R2C cells. Furthermore, GA induced overproduction of intracellular reactive oxygen species (ROS), upregulated Bax expression, decreased mitochondrial membrane potential, and triggered mitochondria-mediated cell apoptosis. Consequently, the downstream effector caspase-3 was activated, resulting in Leydig cells apoptosis. Overall, our results showed that GA could damage R2C Leydig cells by the lesion of the ability of progesterone genesis and inducing cells apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Amine content of vaginal fluid from untreated and treated patients with nonspecific vaginitis.

PubMed Central

Chen, K C; Forsyth, P S; Buchanan, T M; Holmes, K K

1979-01-01

We examined the vaginal washings from patients with nonspecific vaginitis (NSV) to seek biochemical markers and possible explanations for the signs and symptoms of this syndrome. Seven amines were identified including methylamine, isobutylamine, putrescine, cadaverine, histamine, tyramine, and phenethylamine. These amines may contribute to the symptoms of NSV and may contribute to the elevated pH of the vaginal discharge. They may also be partly responsible for the "fishy" odor that is characteristic of vaginal discharges from these patients. Among the seven amines, putrescine and cadaverine were the most abundant and were present in all vaginal discharges from each of ten patients before treatment. These amines are produced in vitro during growth of mixed vaginal bacteria in chemically defined medium, presumably by decarboxylation of the corresponding amino acids. We hypothesize the anaerobic vaginal organisms, previously shown to be quantitatively increased in NSV, are responsible for the amine production, because metronidazole inhibited the production of amines by vaginal bacteria in vitro, and Haemophilus vaginalis did not produce amines. H. vaginalis did release high concentrations of pyruvic acid and of amino acids during growth in peptone-starch-dextrose medium, whereas, other vaginal flora consumed both pyruvic acid and amino acids in the same medium during growth. These findings suggest that a symbiotic relationship may exist between H. vaginalis and other vaginal flora in patients with NSV. Images PMID:447831

Vaginal orgasm is associated with vaginal (not clitoral) sex education, focusing mental attention on vaginal sensations, intercourse duration, and a preference for a longer penis.

PubMed

Brody, Stuart; Weiss, Petr

2010-08-01

Evidence was recently provided for vaginal orgasm, orgasm triggered purely by penile-vaginal intercourse (PVI), being associated with better psychological functioning. Common sex education and sexual medicine approaches might undermine vaginal orgasm benefits. To examine the extent to which women's vaginal orgasm consistency is associated with (i) being told in childhood or adolescence that the vagina was the important zone for inducing female orgasm; (ii) how well they focus mentally on vaginal sensations during PVI; (iii) greater PVI duration; and (iv) preference for above-average penis length.   In a representative sample of the Czech population, 1,000 women reported their vaginal orgasm consistency (from never to almost every time; only 21.9% never had a vaginal orgasm), estimates of their typical foreplay and PVI durations, what they were told in childhood and adolescence was the important zone for inducing female orgasm, their degree of focus on vaginal sensations during PVI, and whether they were more likely to orgasm with a longer than average penis. The association of vaginal orgasm consistency with the predictors noted above. Vaginal orgasm consistency was associated with all hypothesized correlates. Multivariate analysis indicated the most important predictors were being educated that the vagina is important for female orgasm, being mentally focused on vaginal sensations during PVI, and in some analyses duration of PVI (but not foreplay) and preferring a longer than average penis. Focusing attention on penile-vaginal sensation supports vaginal orgasm and the myriad benefits thereof. Brody S, and Weiss P. Vaginal orgasm is associated with vaginal (not clitoral) sex education, focusing mental attention on vaginal sensations, intercourse duration, and a preference for a longer penis. © 2009 International Society for Sexual Medicine.

Safety, efficacy, and tolerability of differential treatment to prevent and treat vaginal dryness and vulvovaginitis in diabetic women.

PubMed

Carati, D; Zizza, A; Guido, M; De Donno, A; Stefanizzi, R; Serra, R; Romano, I; Ouedraogo, C; Megha, M; Tinelli, A

2016-01-01

Problems affecting the vaginal tract in diabetic women are very often neglected. The efficacy and safety of three gynecological treatments in diabetic women have been assessed. A single-blind randomized progressive trial on 48 diabetic women affected by vaginal dryness, dyspareunia, and recurrent Candida infections was carried out. The ICIQ Vaginal Symptoms (ICIQ-VS) questionnaire was administered. The analysis of the parameters of ICIQ-VS questionnaire among the three groups showed significant difference only for "dragging pain" (p = 0.0 19) and "soreness" (p = 0.028). In all groups and for all parameters of the questionnaire, improvement of symptoms was observed. In particular, in Group 1 for all symptoms a highly significant difference was observed, to support the already known benefits of the products and of the proposed combination. Significant improvement was also observed in Group 2. The proposed treatment with DermoXEN® Ultracalming Special for diabetics and DermoXEN® Vitexyl vaginal gel exert effective moisturizing and soothing action. Indeed, the aforementioned products have been proven effective for the main gynecological problems of diabetic women.

Vaginal cysts

MedlinePlus

... essential to determine what type of cyst or mass you may have. A mass or bulge of the vaginal wall may be ... to rule out vaginal cancer, especially if the mass appears to be solid. If the cyst is ...

Menopause and the vaginal microbiome.

PubMed

Muhleisen, Alicia L; Herbst-Kralovetz, Melissa M

2016-09-01

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Office gel sonovaginography for the prediction of posterior deep infiltrating endometriosis: a multicenter prospective observational study.

PubMed

Reid, S; Lu, C; Hardy, N; Casikar, I; Reid, G; Cario, G; Chou, D; Almashat, D; Condous, G

2014-12-01

To use office gel sonovaginography (SVG) to predict posterior deep infiltrating endometriosis (DIE) in women undergoing laparoscopy. This was a multicenter prospective observational study carried out between January 2009 and February 2013. All women were of reproductive age, had a history of chronic pelvic pain and underwent office gel SVG assessment for the prediction of posterior compartment DIE prior to laparoscopic endometriosis surgery. Gel SVG findings were compared with laparoscopic findings to determine the diagnostic accuracy of office gel SVG for the prediction of posterior compartment DIE. In total, 189 women underwent preoperative gel SVG and laparoscopy for endometriosis. At laparoscopy, 57 (30%) women had posterior DIE and 43 (23%) had rectosigmoid/anterior rectal DIE. For the prediction of rectosigmoid/anterior rectal (i.e. bowel) DIE, gel SVG had an accuracy of 92%, sensitivity of 88%, specificity of 93%, positive predictive value (PPV) of 79%, negative predictive value (NPV) of 97%, positive likelihood ratio (LR+) of 12.9 and negative likelihood ratio (LR-) of 0.12 (P = 3.98E-25); for posterior vaginal wall and rectovaginal septum (RVS) DIE, respectively, the accuracy was 95% and 95%, sensitivity was 18% and 18%, specificity was 99% and 100%, PPV was 67% and 100%, NPV was 95% and 95%, LR+ was 32.4 and infinity and LR- was 0.82 and 0.82 (P = 0.009 and P = 0.003). Office gel SVG appears to be an effective outpatient imaging technique for the prediction of bowel DIE, with a higher accuracy for the prediction of rectosigmoid compared with anterior rectal DIE. Although the sensitivity for vaginal and RVS DIE was limited, gel SVG had a high specificity and NPV for all forms of posterior DIE, indicating that a negative gel SVG examination is highly suggestive of the absence of DIE at laparoscopy. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study.

PubMed

Gao, Weijiao; Weng, Jinlong; Gao, Yunong; Chen, Xiaochi

2013-06-10

The female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota. A total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects. We found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles. Our study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.

Prevalence of vaginal candidiasis among pregnant women with abnormal vaginal discharge in Maiduguri.

PubMed

Ibrahim, S M; Bukar, M; Mohammed, Y; Mohammed, B; Yahaya, M; Audu, B M; Ibrahim, H M; Ibrahim, H A

2013-01-01

Pregnancy represents a risk factor in the occurrence of vaginal candidiasis. To determine the prevalence and clinical features associated with abnormal vaginal discharge and C. albicans infection in pregnant women. High vaginal swab samples and data on epidemiological characteristics were collected from 400 pregnant women with complaints of abnormal vaginal discharge at booking clinic of University of Maiduguri Teaching Hospital. The data was analysed using SPSS 16.0 statistical software. The prevalence of abnormal vaginal discharge in pregnancy was 31.5%. The frequency of abnormal vaginal discharge was 183 (45.8%) among those aged 20-24 years, 291 (72.8%) in multipara, 223 (55.8%) in those with Primary education and 293 (73.2%) in unemployed. Vulval pruritus 300 (75.0%) was significantly related to abnormal vaginal discharge (P < 0.001). The prevalence of C. albicans was 41%. The frequencies of Vulval itching, Dyspareunia and vulval excoriation among those with candidiasis were 151 (50.3%), 14 (56.0%) and 75 (75.0%) respectively (P < 0.001). The prevalence of abnormal vaginal discharge in pregnancy was high in this study and C. albicans was the commonest cause. It is recommended that a pregnant woman complaining of abnormal vaginal discharge be assessed and Laboratory diagnosis done in order to give appropriate treatment.

Progesterone is essential for maintenance and growth of uterine leiomyoma.

PubMed

Ishikawa, Hiroshi; Ishi, Kazutomo; Serna, Vanida Ann; Kakazu, Rafael; Bulun, Serdar E; Kurita, Takeshi

2010-06-01

Uterine leiomyomata (ULs) represent the most common tumor in women and can cause abnormal uterine bleeding, large pelvic masses, and recurrent pregnancy loss. Although the dependency of UL growth on ovarian steroids is well established, the relative contributions of 17beta-estradiol and progesterone are yet to be clarified. Conventionally, estradiol has been considered the primary stimulus for UL growth, and studies with cell culture and animal models support this concept. In contrast, no research model has clearly demonstrated a requirement of progesterone in UL growth despite accumulating clinical evidence for the essential role of progesterone in this tumor. To elucidate the functions of ovarian steroids in UL, we established a xenograft model reflecting characteristics of these tumors by grafting human UL tissue beneath the renal capsule of immunodeficient mice. Leiomyoma xenografts increased in size in response to estradiol plus progesterone through cell proliferation and volume increase in cellular and extracellular components. The xenograft growth induced by estradiol plus progesterone was blocked by the antiprogestin RU486. Furthermore, the volume of established UL xenografts decreased significantly after progesterone withdrawal. Surprisingly, treatment with estradiol alone neither increased nor maintained the tumor size. Although not mitogenic by itself, estradiol induced expression of progesterone receptor and supported progesterone action on leiomyoma xenografts. Taken together, our findings define that volume maintenance and growth of human UL are progesterone dependent.

Progesterone down-regulates SLIT/ROBO expression in mouse corpus luteum.

PubMed

Zhang, Xuejing; Mi, Meiyan; Hao, Weili; Fan, Qiongying; Gao, Bulang

2017-09-01

Progesterone produced by the corpus luteum (CL) is essential for preparation, implantation and maintenance of gestation. Furthermore, progesterone plays a protective role against luteolysis in rodents. It has been reported that Slit/Robo family members expressed in the CL and involved in prostaglandin F 2α (PGF 2α ) induced luteolysis. However, the interactions between progesterone and Slits/Robos in CL are not clear. This study was designed to examine whether or not luteolysis is regulated by the interaction of progesterone and Slits/Robos in mouse CL. In the current study, we used Real-time PCR to identify the effect of progesterone on Slit2/Robo1 expression in cultured luteal cells in vitro, and the exogenous progesterone injection on mouse luteolysis and Slit/Robo expression in vivo was studied via Real-time PCR and Western bolt. Our in vitro experiment revealed that 1μM progesterone significantly decreased Slit2/Robo1 mRNA levels at 6h, 12h and 24h. Our in vivo experiment showed that the mRNA and protein levels of Slit2 and Robo1 decreased significantly 7days after progesterone supplement. These findings indicate that progesterone maintains CL function and resists luteolysis possibly through down-regulating Slit/Robo signaling pathway in the CL. Copyright © 2017 Elsevier GmbH. All rights reserved.

Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans.

PubMed

Halwes, Michael E; Steinbach-Rankins, Jill M; Frieboes, Hermann B

2016-10-10

Although a number of drugs have been developed for the treatment and prevention of human immunodeficiency virus (HIV) infection, it has proven difficult to optimize the drug and dosage parameters. The vaginal tissue, comprised of epithelial, stromal and blood compartments presents a complex system which challenges evaluation of drug kinetics solely through empirical effort. To provide insight into the underlying processes, mathematical modeling and computational simulation have been applied to the study of retroviral microbicide pharmacokinetics. Building upon previous pioneering work that modeled the delivery of Tenofovir (TFV) via topical delivery to the vaginal environment, here we computationally evaluate the performance of the retroviral inhibitor dapivirine released from a microbicide gel. We adapt the TFV model to simulate the multicompartmental diffusion and uptake of dapivirine into the blood plasma and vaginal compartments. The results show that dapivirine is expected to accumulate at the interface between the gel and epithelium compartments due to its hydrophobic characteristics. Hydrophobicity also results in decreased diffusivity, which may impact distribution by up to 2 orders of magnitude compared to TFV. Maximum concentrations of dapivirine in the epithelium, stroma, and blood were 9.9e7, 2.45e6, and 119pg/mL, respectively. This suggests that greater initial doses or longer time frames are required to obtain higher drug concentrations in the epithelium. These observations may have important ramifications if a specific time frame is required for efficacy, or if a minimum/maximum concentration is needed in the mucus, epithelium, or stroma based on combined efficacy and safety data. Copyright © 2016 Elsevier B.V. All rights reserved.

Women's preferences for vaginal antimicrobial contraceptives. III. Choice of a formulation, applicator, and packaging.

PubMed

Hardy, E; Jiménez, A L; de Pádua, K S; Zaneveld, L J

1998-10-01

Novel vaginal formulations are under development to combat the increasing incidence of sexually transmitted diseases, including AIDS, and also unplanned pregnancies. A study was performed to determine women's preferences for different dosage forms (gel, cream, ovule/suppository, film, foam, tablet), width, length, and color of an applicator, and various types of packages. The study was conducted in Campinas, Brazil. A total of 635 women were interviewed, including both adolescents and adults and low and middle-high socioeconomic groups. The large majority of the women preferred a gel over a cream; both were preferred over the other methods. When asked which method they would not use, the film was most frequently identified, followed by the tablet and ovule. The primary reasons for selecting a particular dosage form were ease of use, absence of odor or the presence of a pleasant one, absence of color, and insertion with an applicator. The major reasons for not using a method were discomfort, "plastic" appearance, distrust of effectiveness, difficulty with insertion, messiness, and rigidity/hardness. The majority of the women liked the applicator shown. The prefilled single dose applicator was by far the preferred packaging. This information should aid in the development of consumer-friendly, vaginal formulations.

Progesterone Modulates a Neuronal Nicotinic Acetylcholine Receptor

NASA Astrophysics Data System (ADS)

Valera, S.; Ballivet, M.; Bertrand, D.

1992-10-01

The major brain nicotinic acetylcholine receptor is assembled from two subunits termed α 4 and nα 1. When expressed in Xenopus oocytes, these subunits reconstitute a functional acetylcholine receptor that is inhibited by progesterone levels similar to those found in serum. In this report, we show that the steroid interacts with a site located on the extracellular part of the protein, thus confirming that inhibition by progesterone is not due to a nonspecific perturbation of the membrane bilayer or to the activation of second messengers. Because inhibition by progesterone does not require the presence of agonist, is voltage-independent, and does not alter receptor desensitization, we conclude that the steroid is not an open channel blocker. In addition, we show that progesterone is not a competitive inhibitor but may interact with the acetylcholine binding site and that its effect is independent of the ionic permeability of the receptor.

Fabrication of Progesterone-Loaded Nanofibers for the Drug Delivery Applications in Bovine

NASA Astrophysics Data System (ADS)

Karuppannan, Chitra; Sivaraj, Mehnath; Kumar, J. Ganesh; Seerangan, Rangasamy; Balasubramanian, S.; Gopal, Dhinakar Raj

2017-02-01

Progesterone is a potent drug for synchronization of the estrus and ovulation cycles in bovine. At present, the estrus cycle of bovine is controlled by the insertion of progesterone-embedded silicone bands. The disadvantage of nondegradable polymer inserts is to require for disposal of these bands after their use. The study currently focuses on preparation of biodegradable progesterone-incorporated nanofiber for estrus synchronization. Three different concentrations (1.2, 1.9, and 2.5 g) of progesterone-impregnated nanofibers were fabricated using electrospinning. The spun membrane were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Uniform surface morphology, narrow size distribution, and interaction between progesterone and zein were confirmed by SEM. FTIR spectroscopy indicated miscibility and interaction between zein and progesterone. X-ray analysis indicated that the size of zein crystallites increased with progesterone content in nanofibers. Significant differences in thermal behavior of progesterone-impregnated nanofiber were observed by DSC. Cell viability studies of progesterone-loaded nanofiber were examined using MTT assay. In vitro release experiment is to identify the suitable progesterone concentration for estrus synchronization. This study confirms that progesterone-impregnated nanofibers are an ideal vehicle for progesterone delivery for estrus synchronization of bovines.

Vaginal Fistula

MedlinePlus

Vaginal fistula Overview A vaginal fistula is an abnormal opening that connects your vagina to another organ, such as your bladder, colon or rectum. Your ... describe the condition as a hole in your vagina that allows stool or urine to pass through ...

Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women: a clinical trial study.

PubMed

Seyyedi, Fatemeh; Kopaei, Mahmoud Rafiean; Miraj, Sepideh

2016-11-01

This study was conducted to evaluate the therapeutic effects of vaginal royal jelly and vaginal estrogen on quality of life and vaginal atrophy in postmenopausal women. This double-blind randomized controlled clinical trial was carried out at gynecology and obstetrics clinics of Hajar Hospital of Shahrekord University of Medical Sciences (Iran) from January 2013 to January 2014. The study was conducted on married postmenopausal women between 50 and 65 years old. Of 120 patients, 30 individuals were excluded based on the exclusion criteria, and 90 women were randomly distributed into three groups of 30 royal jelly vaginal cream 15%, vaginal Premarin, and placebo (lubricant), for three months. At the beginning and the end of the study, quality of life and vaginal cytology assay were evaluated. Data were analyzed by SPSS Version 11. Vaginal cream of royal jelly is significantly more effective than vaginal cream of Premarin and lubricant in improvement of quality of life in postmenopausal women (p<0.05). Moreover, Pap smear results showed that vaginal atrophy in vaginal Premarin group was lower than the other groups (p<0.001), and there was no significant difference between lubricant and royal jelly groups (p=0.89). Administration of vaginal royal jelly was effective in quality-of-life improvement of postmenopausal women. Given to the various properties of royal jelly and its effectiveness on quality of life and vaginal atrophy in postmenopausal women, further studies are recommended for using =royal jelly in improving menopausal symptoms. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT code: 2014112220043n1. Shahrekord University of Medical Sciences supported this research (project no. 1440).

Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression in Human Myometrial Cells: Implications for Progesterone Actions in Human Pregnancy and Parturition

PubMed Central

Tan, Huiqing; Yi, Lijuan; Rote, Neal S.; Hurd, William W.

2012-01-01

Context: Progesterone promotes uterine relaxation during pregnancy and its withdrawal induces labor. Progesterone withdrawal in human parturition is mediated in part by changes in the relative levels of the nuclear progesterone receptor isoforms, PR-A and PR-B, in myometrial cells. Parturition also involves myometrial inflammation; however, the functional link between nuclear PR-mediated progesterone actions and inflammation in human myometrial cells is unclear. Objective: Our objective was to determine how PR-A and PR-B regulate progesterone action in human myometrial cells and specifically the expression of genes encoding contraction-associated proteins and proinflammatory mediators. Design: Effects of PR-A and PR-B on the capacity for progesterone to modulate gene expression was determined using an immortalized human myometrial cell line stably transfected with inducible PR-A and PR-B expression transgenes and conditioned to express various PR-A and PR-B levels. Gene expression was assessed by genome wide transcriptome analysis, quantitative RT-PCR and immunoblotting. Results: PR-A and PR-B were each transcriptionally active in response to progesterone and affected the expression of distinct gene cohorts. The capacity for progesterone to affect gene expression was dependent on the PR-A to PR-B ratio. This was especially apparent for the expression of proinflammatory genes. Progesterone decreased proinflammatory gene expression when the PR-A to PR-B ratio favored PR-B and increased proinflammatory gene expression when the ratio favored PR-A. Progesterone via PR-B increased expression of inhibitor-κBα, a repressor of the nuclear factor-κB transcription factor, and inhibited basal and lipopolysaccharide-induced proinflammatory gene expression. Both of those PR-B-mediated effects were inhibited by PR-A. Conclusions: Our data suggest that during most of human pregnancy, when myometrial cells are PR-B dominant, progesterone promotes myometrial quiescence through PR

1,3-Dichloro-2-propanol inhibits progesterone production through the expression of steroidogenic enzymes and cAMP concentration in Leydig cells.

PubMed

Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Li, Guoqiang; Hu, Yunfeng; Li, Mingwei; Yan, Rian; Su, Zhijian; Huang, Yadong

2014-07-01

1,3-Dichloro-2-propanol (1,3-DCP) is a well-known food processing contaminant that has been shown to impede male reproductive function. However, its mechanism of action remains elusive. In this study, the effects of 1,3-DCP on progesterone production were investigated using the R2C Leydig cell model. 1,3-DCP significantly reduced cell viability from 7.48% to 97.4% at doses comprised between 0.5 and 6mM. Single cell gel/comet assays and atomic force microscopy assays showed that 1,3-DCP induced early phase cell apoptosis. In addition, 1,3-DCP significantly reduced progesterone production detected by radioimmunoassay (RIA). The results from quantitative polymerase chain reaction and western blotting demonstrated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase were significantly down-regulated in R2C cells. Particularly, the change rhythm of Star expression was highly consistent with progesterone production. Furthermore, the cyclic adenosine monophosphate (cAMP) and the mitochondrial membrane potential mediated by ROS, which are involved in regulating progesterone synthesis were also decreased in response to the 1,3-DCP treatment. Overall, the data presented here suggested that 1,3-DCP interferes with the male steroidogenic capacity mainly by down-regulating the level of cAMP and the key enzymes involved in the androgen synthesis pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Rational Design and Development of A Dual Chamber Vaginal/Rectal Microbicide Gel Formulation for HIV Prevention

PubMed Central

Ham, Anthony S.; Nugent, Sean T.; Peters, Jennifer J.; Katz, David F.; Shelter, Cory M.; Dezzutti, Charlene S.; Boczar, Ashlee D.; Buckheit, Karen W.; Buckheit, Robert W.

2015-01-01

The DuoGel™ was developed for safe and effective dual chamber administration of antiretroviral drugs to reduce the high incidence of HIV transmission during receptive vaginal and anal intercourse. The DuoGel™s containing IQP-0528, a non-nucleoside reverse transcriptase inhibitor (NNRTI), were formulated from GRAS excipients approved for vaginal and rectal administration. The DuoGel™s were evaluated based upon quantitative physicochemical and biological evaluations defined by a Target Product Profile (TPP) acceptable for vaginal and rectal application. From the two primary TPP characteristics defined to accommodate safe rectal administration three DuoGel™ formulations (IQB3000, IQB3001, and IQB3002) were developed at pH 6.00 and osmolality ≤ 400 mmol/kg. The DuoGel™s displayed no in vitro cellular or bacterial toxicity and no loss in viability in ectocervical and colorectal tissue. IQB3000 was removed from consideration due to reduced NNRTI delivery (~65% reduction) and IQB3001 was removed due to increase spread resulting in leakage. IQB3002 containing IQP-0528 was defined as our lead DuoGel™ formulation, possessing potent activity against HIV-1 (EC50 = 10 nM). Over 12 month stability evaluations, IQB3002 maintained formulation stability. This study has identified a lead DuoGel™ formulation that will safely deliver IQP-0528 to prevent sexual HIV-1 transmission in the vagina and rectum. PMID:26093158

Vaginal lactobacilli profile in pregnant women with normal & abnormal vaginal flora.

PubMed

Yeruva, Thirupathaiah; Rajkumar, Hemalatha; Donugama, Vasundhara

2017-10-01

Lactobacilli species that are better adapted to vaginal environment of women may colonize better and offer protection against vaginal pathogenic bacteria. In this study, the distribution of common Lactobacillus species was investigated in pregnant women. Sixty seven pregnant women were included in the study and vaginal samples were collected for Gram staining. Women were classified as normal vaginal flora, intermediate flora and bacterial vaginosis (BV) based on Nugent's score. Vaginal samples were also collected for the identification of Lactobacillus spp. by multiplex polymerase chain reaction (PCR) profiling of 16S rDNA amplification method. Lactobacillus crispatus (100%) was the most predominant Lactobacillus spp. present in pregnant women with normal flora, followed by L. iners (77%), L. jensenii (74%) and L. helveticus (60%). While, L. iners was commonly present across groups in women with normal, intermediate or BV flora, L. crispatus, L. jensenii and L. helveticus decreased significantly as the vaginal flora changed to intermediate and BV. In women with BV, except L. iners other species of lactobacilli was less frequently prevalent. Species such as L. rhamnosus, L. fermentum, L. paracasei and L. casei were not detected in any vaginal sample. L. crispatus, L. jensinii and L. helveticus were predominant species in women with normal flora. L. crispatus alone or in combination with L. jensinii and L. helveticus may be evaluated for probiotic properties for the prevention and treatment of BV.

Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

PubMed Central

Nelson, Tiffanie M.; Borgogna, Joanna-Lynn C.; Brotman, Rebecca M.; Ravel, Jacques; Walk, Seth T.; Yeoman, Carl J.

2015-01-01

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a “fishy” odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria. PMID:26483694

Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

PubMed

Nelson, Tiffanie M; Borgogna, Joanna-Lynn C; Brotman, Rebecca M; Ravel, Jacques; Walk, Seth T; Yeoman, Carl J

2015-01-01

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a "fishy" odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria.

Vaginal bleeding in pregnancy

MedlinePlus

Pregnancy - vaginal bleeding; Maternal blood loss - vaginal ... Up to 1 in 4 women have vaginal bleeding at some time during their pregnancy. Bleeding is more common in the first 3 months (first trimester), especially with twins.

Vaginitis: diagnosis and management.

PubMed

Faro, S

1996-01-01

The various conditions that give rise to vaginitis include specific and nonspecific entities, such as candidiasis, trichomoniasis, bacterial vaginosis, group B streptococcal vaginitis, purulent vaginitis, volvodynia, and vestibulitis. The patient with chronic vaginitis usually develops this condition because of a misdiagnosis. It is critical that patients who have chronic vaginitis be thoroughly evaluated to determine if there is a specific etiology and whether their condition is recurrent or persistent, or is a reinfection. This also must include obtaining a detailed history, beginning with the patient's best recollection of when she felt perfectly normal. The physician must have an understanding of a healthy vaginal ecosystem and what mechanisms are in place to maintain the equilibrium. The vaginal ecosystem is a complex system of micro-organisms interacting with host factors to maintain its equilibrium. The endogenous microflora consists of a variety of bacteria, which include aerobic, facultative and obligate anaerobic bacteria. These organisms exist in a commensal, synergistic or antagonistic relationship. Therefore, it is important to understand what factors control the delicate equilibrium of the vaginal ecosystem, and which factors, both endogenous and exogenous, can disrupt this system. It is also important for the physician to understand that when a patient has symptoms of vaginitis it is not always due to an infectious etiology. There are situations in which an inflammatory reaction occurs but the specific etiology may not be determined. Thus, it is important that the physician not rush through the history or the examination.

Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women: a clinical trial study

PubMed Central

Seyyedi, Fatemeh; Kopaei, Mahmoud Rafiean; Miraj, Sepideh

2016-01-01

Objective This study was conducted to evaluate the therapeutic effects of vaginal royal jelly and vaginal estrogen on quality of life and vaginal atrophy in postmenopausal women. Methods This double-blind randomized controlled clinical trial was carried out at gynecology and obstetrics clinics of Hajar Hospital of Shahrekord University of Medical Sciences (Iran) from January 2013 to January 2014. The study was conducted on married postmenopausal women between 50 and 65 years old. Of 120 patients, 30 individuals were excluded based on the exclusion criteria, and 90 women were randomly distributed into three groups of 30 royal jelly vaginal cream 15%, vaginal Premarin, and placebo (lubricant), for three months. At the beginning and the end of the study, quality of life and vaginal cytology assay were evaluated. Data were analyzed by SPSS Version 11. Results Vaginal cream of royal jelly is significantly more effective than vaginal cream of Premarin and lubricant in improvement of quality of life in postmenopausal women (p<0.05). Moreover, Pap smear results showed that vaginal atrophy in vaginal Premarin group was lower than the other groups (p<0.001), and there was no significant difference between lubricant and royal jelly groups (p=0.89). Conclusion Administration of vaginal royal jelly was effective in quality-of-life improvement of postmenopausal women. Given to the various properties of royal jelly and its effectiveness on quality of life and vaginal atrophy in postmenopausal women, further studies are recommended for using =royal jelly in improving menopausal symptoms. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT code: 2014112220043n1. Funding Shahrekord University of Medical Sciences supported this research (project no. 1440). PMID:28070251

Vaginal Cancer—Health Professional Version

Cancer.gov

Vaginal cancer is often squamous cell carcinoma. Other types of vaginal cancer are adenocarcinoma, melanoma, and sarcoma. Infection with certain types of human papillomavirus (HPV) causes most vaginal cancer. Find evidence-based information on vaginal cancer treatment and research.

Increasing the Effectiveness of Vaginal Microbicides: A Biophysical Framework to Rethink Behavioral Acceptability

PubMed Central

Verguet, Stéphane; Young Holt, Bethany; Szeri, Andrew J.

2010-01-01

Background Microbicide candidates delivered via gel vehicles are intended to coat the vaginal epithelium after application. The coating process depends on intrinsic biophysical properties of the gel texture, which restricts the potential choices for an effective product: the gel first must be physically synthesizable, then acceptable to the user, and finally applied in a manner promoting timely adequate coating, so that the user adherence is optimized. We present a conceptual framework anchoring microbicide behavioral acceptability within the fulfillment of the product biophysical requirements. Methods We conducted a semi-qualitative/quantitative study targeting women aged 18–55 in Northern California to assess user preferences for microbicide gel attributes. Attributes included: (i) the wait time between application and intercourse, (ii) the gel texture and (iii) the trade-off between wait time and gel texture. Wait times were assessed using a mathematical model determining coating rates depending upon the gel's physical attributes. Results 71 women participated. Results suggest that women would independently prefer a gel spreading rapidly, in 2 to 15 minutes (P<0.0001), as well as one that is thick or slippery (P<0.02). Clearly, thick gels do not spread rapidly; hence the motivation to study the trade-off. When asked the same question ‘constrained’ by the biophysical reality, women indicated no significant preference for a particular gel thickness (and therefore waiting time) (P>0.10) for use with a steady partner, a preference for a watery gel spreading rapidly rather than one having intermediate properties for use with a casual partner (P = 0.024). Conclusions Biophysical constraints alter women's preferences regarding acceptable microbicide attributes. Product developers should offer a range of formulations in order to address all preferences. We designed a conceptual framework to rethink behavioral acceptability in terms of biophysical requirements

Progesterone biotransformation by plant cell suspension cultures.

PubMed Central

Yagen, B; Gallili, G E; Mateles, R I

1978-01-01

Progesterone was converted to 5alpha-pregnane-3alpha-ol-20-one, delta4-pregnene-20alpha-ol-3-one, delta4-pregnene-14alpha-ol-3,20-dione, delta4-pregnene-7beta,14alpha-diol-3,20-dione, and delta4-pregnene-6beta,11alpha-diol-3,20-dione by cell cultures of Lycopersicon esculentum. Cell cultures of Capsicum frutescens (green) metabolized progesterone to delta4-pregnene-20alpha-ol-3-one in very high yield, and Vinca rosea yielded delta4-pregnene-20beta-ol-3-one and delta4-pregnene-14alpha-ol-3,20-dione. A stereospecific reduction of the keto groups and a double bond and stereospecific introduction of hydroxyl groups at the 6, 11, and 14 positions have been observed. The mono- and dihydroxylated progesterones have not previously been reported as metabolic products of progesterone by plant cell systems and represent de novo hydroxylation of a nonglycosylated steroid. PMID:697360

Comparison of vaginal microbial community structure in healthy and endometritis dairy cows by PCR-DGGE and real-time PCR.

PubMed

Wang, Jun; Sun, Chengtao; Liu, Chang; Yang, Yujiang; Lu, Wenfa

2016-04-01

The normal vaginal microflora provides protection against infections of the reproductive tract. Previous studies have focused on the isolation and screening of probiotic strains from the vagina of cows; however, the vaginal microflora of postpartum cows is poorly characterized. The present study was conducted to evaluate and characterize the vaginal microflora of healthy postpartum cows in relation to postpartum cows with endometritis by using PCR followed by denaturing gradient gel electrophoresis (PCR-DGGE) and Real-time PCR. The study population comprised 5 healthy cows and 5 cows with endometritis. The results indicated that the vaginal bacterial microflora of healthy postpartum cows was dominated by Lactobacillus sakei subsp. and Weissella koreensis, while there were no dominant bacterial species in the vaginal microflora of postpartum cows with endometritis. Common microorganisms such as Bacteroides spp., Fusobacterium spp., Enterococcus spp., Prevotella spp., Clostridium perfringens strains, and Escherichia coli were detected in both groups of cows by Real-time PCR. The bacterial diversity in the vagina of cows with endometritis was significantly higher than that in healthy cows. The results indicated that the vaginal microflora of cows with endometritis was more diverse and lacked dominant bacterial species as compared to that of the healthy cows, suggesting that disruption of the normal vaginal microflora may contribute to the onset of endometritis. This microbial community analysis provided information that might be used to develop probiotics to treat endometritis in cows; however, further investigation is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selective progesterone receptor modulators 1: use during pregnancy.

PubMed

Benagiano, Giuseppe; Bastianelli, Carlo; Farris, Manuela

2008-10-01

A large number of synthetic compounds known as selective progesterone receptor modulators can bind to progesterone receptors: the ligands exhibit a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism. Only a dozen or so selective progesterone receptor modulators have been tested to any significant extent: among them are mifepristone (RU 486), asoprisnil (J867), onapristone (ZK 98 299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710. Their clinical applications during pregnancy are discussed. A careful evaluation of existing major review papers and recently published articles was carried out focusing on mifepristone, the most widely studied selective progesterone receptor modulator, which was first used for the voluntary interruption of an early gestation. Other selective progesterone receptor modulators, especially those with partial agonist action, have shown little activity during pregnancy in animal models. Besides early and late voluntary interruption of gestation, selective progesterone receptor modulators have been tested in a variety of obstetrical situations: to obtain a ripening of the cervix, for the medical management of early embryonic loss and foetal death, for the induction of labour at term and for the medical treatment of extra-uterine pregnancies. The only applications that seem worthy of large-scale utilisation during pregnancy are voluntary interruption of early and late gestation, medical management of early delayed miscarriage and late foetal demise.

Selective progesterone receptor modulators 2: use in reproductive medicine.

PubMed

Benagiano, Giuseppe; Bastianelli, Carlo; Farris, Manuela

2008-10-01

Synthetic compounds can bind to progesterone receptors and these progesterone receptor ligands exhibit a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism. These substances have been classified as antiprogestins or as selective progesterone receptor modulators. There are several hundred selective progesterone receptor modulators available, although only a dozen or so have been evaluated to any significant extent. The best-known selective progesterone receptor modulators are mifepristone (RU 486), asoprisnil (J 867), onapristone (ZK 98299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710. A careful evaluation of existing major review papers and of recently published articles was carried out for the indications under review, focusing not only on mifepristone, but also on those other selective progesterone receptor modulators for which data are available. Outside pregnancy, selective progesterone receptor modulators are used or have been tested clinically for a number of indications in reproductive medicine: as oral contraceptives, alone or in combination with a progestin, to improve cycle control in users of progestin-only contraceptives, as emergency contraceptives, for the medical treatment of uterine fibroids, in cases of endometriosis and premenstrual syndrome and to improve ovarian stimulation prior to in vitro fertilisation. In the authors' opinion, as of today, few applications outside pregnancy seem worthy of large-scale use: emergency contraception and long-term medical management of uterine fibroids and possibly of endometriosis.

Vaginal Cancer

MedlinePlus

Vaginal cancer is a rare type of cancer. It is more common in women 60 and older. You are also more likely to get it if you have had a human ... test can find abnormal cells that may be cancer. Vaginal cancer can often be cured in its ...

The effect of vaginal cream containing ginger in users of clotrimazole vaginal cream on vaginal candidiasis.

PubMed

Shabanian, Sheida; Khalili, Sima; Lorigooini, Zahra; Malekpour, Afsaneh; Heidari-Soureshjani, Saeid

2017-01-01

Vulvovaginal candidiasis is one of the most common infections of the genital tract in women that causes many complications. Therefore, we examined the clinical effect of ginger cream along with clotrimazole compared to vaginal clotrimazole alone in this study. This double-blind clinical trial was conducted on 67 women admitted to the Gynecology Clinic of Hajar Hospital with vaginal candidiasis. The patients were divided randomly into two groups of 33 and 34 people. The diagnosis was made according to clinical symptoms, wet smear, and culture. Ginger-clotrimazole vaginal cream 1% and clotrimazole vaginal cream 1% were administered to groups 1 and 2, respectively, once a day for 7 days and therapeutic effects and symptoms were evaluated in readmission. Data analysis was performed using SPSS version 22, t -test and Chi-square. The mean value of variables itching ( P > 0.05), burning ( P > 0.05), and cheesy secretion ( P < 0.05) in users of ginger-clotrimazole was less than the other group after the treatment. Recurrence in clotrimazole group was 48.5% and in ginger-clotrimazole group 51.2% during the 1-month follow-up with no significant difference. Study results showed that cream containing ginger and clotrimazole 1% was more effective and may be more useful than the clotrimazole to treat vaginal candidiasis.

Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells.

PubMed

Patel, Mickey V; Fahey, John V; Rossoll, Richard M; Wira, Charles R

2013-05-01

Vaginal epithelial cells (VEC) are the first line of defense against incoming pathogens in the female reproductive tract. Their ability to produce the anti-HIV molecules elafin and HBD2 under hormonal stimulation is unknown. Vaginal epithelial cells were recovered using a menstrual cup and cultured overnight prior to treatment with estradiol (E₂), progesterone (P₄) or a panel of selective estrogen response modulators (SERMs). Conditioned media were recovered and analyzed for protein concentration and anti-HIV activity. E₂ significantly decreased the secretion of HBD2 and elafin by VEC over 48 hrs, while P4 and the SERMs (tamoxifen, PHTTP, ICI or Y134) had no effect. VEC conditioned media from E₂ -treated cells had no anti-HIV activity, while that from E₂ /P₄ -treated cells significantly inhibited HIV-BaL infection. The menstrual cup allows for effective recovery of primary VEC. Their production of HBD2 and elafin is sensitive to E₂, suggesting that innate immune protection varies in the vagina across the menstrual cycle. © 2013 John Wiley & Sons A/S.

Innate Immunity in the Vagina (Part I): Estradiol Inhibits HBD2 and Elafin Secretion by Human Vaginal Epithelial Cells

PubMed Central

Patel, Mickey V.; Fahey, John V.; Rossoll, Richard M.; Wira, Charles R.

2013-01-01

Problem Vaginal epithelial cells (VEC) are the first line of defense against incoming pathogens in the female reproductive tract. Their ability to produce the anti-HIV molecules elafin and HBD2 under hormonal stimulation is unknown. Method of study Vaginal epithelial cells were recovered using a menstrual cup and cultured overnight prior to treatment with estradiol (E2), progesterone (P4) or a panel of selective estrogen response modulators (SERMs). Conditioned media were recovered and analyzed for protein concentration and anti-HIV activity. Results E2 significantly decreased the secretion of HBD2 and elafin by VEC over 48 hrs, while P4 and the SERMs (tamoxifen, PHTTP, ICI or Y134) had no effect. VEC conditioned media from E2-treated cells had no anti-HIV activity, while that from E2/P4-treated cells significantly inhibited HIV-BaL infection. Conclusion The menstrual cup allows for effective recovery of primary VEC. Their production of HBD2 and elafin is sensitive to E2, suggesting that innate immune protection varies in the vagina across the menstrual cycle. PMID:23398087

Vaginal mucosal flap as a sling preservation for the treatment of vaginal exposure of mesh.

PubMed

Kim, Sea Young; Park, Jong Yeon; Kim, Han Kwon; Park, Chang Hoo; Kim, Sung Jin; Sung, Gi Teck; Park, Chang Myon

2010-06-01

Tension-free vaginal tape (TVT) procedures are used for the treatment of stress urinary incontinence in women. The procedures with synthetic materials can have a risk of vaginal erosion. We experienced transobturator suburethral sling (TOT) tape-induced vaginal erosion and report the efficacy of a vaginal mucosal covering technique. A total of 560 female patients diagnosed with stress urinary incontinence underwent TOT procedures at our hospital between January 2005 and August 2009. All patients succeeded in follow-ups, among which 8 patients (mean age: 50.5 years) presented with vaginal exposure of the mesh. A vaginal mucosal covering technique was performed under local anesthesia after administration of antibiotics and vaginal wound dressings for 3-4 days. Seven of the 8 patients complained of persistent vaginal discharge postoperatively. Two of the 8 patients complained of dyspareunia of their male partners. The one remaining patient was otherwise asymptomatic, but mesh erosion was discovered at the routine follow-up visit. Six of the 8 patients showed complete mucosal covering of the mesh after the operation (mean follow-up period: 16 moths). Vaginal mucosal erosion recurred in 2 patients, and the mesh was then partially removed. One patient had recurrent stress urinary incontinence. Vaginal mucosal covering as a sling preservation with continued patient continence may be a feasible and effective option for the treatment of vaginal exposure of mesh after TOT tape procedures.

Progesterone inhibits proliferation and modulates expression of proliferation-Related genes in classical progesterone receptor-negative human BxPC3 pancreatic adenocarcinoma cells.

PubMed

Goncharov, Alexey I; Maslakova, Aitsana A; Polikarpova, Anna V; Bulanova, Elena A; Guseva, Alexandra A; Morozov, Ivan A; Rubtsov, Petr M; Smirnova, Olga V; Shchelkunova, Tatiana A

2017-01-01

Recent studies suggest that progesterone may possess anti-tumorigenic properties. However, a growth-modulatory role of progestins in human cancer cells remains obscure. With the discovery of a new class of membrane progesterone receptors (mPRs) belonging to the progestin and adipoQ receptor gene family, it becomes important to study the effect of this hormone on proliferation of tumor cells that do not express classical nuclear progesterone receptors (nPRs). To identify a cell line expressing high levels of mPRs and lacking nPRs, we examined mRNA levels of nPRs and three forms of mPRs in sixteen human tumor cell lines of different origin. High expression of mPR mRNA has been found in pancreatic adenocarcinoma BxPC3 cells, while nPR mRNA has not been detected in these cells. Western blot analysis confirmed these findings at the protein level. We revealed specific binding of labeled progesterone in these cells with affinity constant similar to that of human mPR expressed in yeast cells. Progesterone at high concentration of 20 μM significantly reduced the mRNA levels of proliferation markers Ki67 and PCNA, as well as of cyclin D1, and increased the mRNA levels of cyclin dependent kinase inhibitors p21 and p27. Progesterone (1 μM and 20 μM) significantly inhibited proliferative activity of BxPC3 cells. These results point to anti-proliferative effects of the progesterone high concentrations on BxPC3 cells and suggest that activation of mPRs may mediate this action. Our data are a starting point for further investigations regarding the application of progesterone in pancreatic cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Progesterone Inhibits Leptin-Induced Invasiveness of BeWo Cells.

PubMed

Jo, Yun Sung; Lee, Gui Se Ra; Nam, Sun Young; Kim, Sa Jin

2015-01-01

This study investigated the roles of progesterone and leptin in placenta invasion, which is closely related to pregnancy prognosis. We examined the effects of leptin and progesterone on the invasion of BeWo cells, a human trophoblastic cell line, and the effect of concurrent treatment. Cells were treated with leptin (0, 5, 50, or 500 ng/mL) or progesterone (0, 2, 20, or 200 µM) and cultured in an invasion assay. Cells treated with 500 ng/mL leptin were also treated with progesterone (0, 2, 20, or 200 µM) in the invasion assay for 48 h. The number of cells that invaded the lower surface was counted in five randomly chosen fields using a light microscope with a 200× objective. The mRNA expression levels of MMP-9, TIMP1, TIMP2, and E-cadherin were detected by semi-quantitative PCR. Invasion of BeWo cells was promoted by leptin and influenced by both leptin concentration and treatment duration. Invasion was most effective at 500 ng/mL leptin and 48 h culture. Leptin-induced invasiveness was suppressed by progesterone in a dose-dependent manner. Leptin significantly decreased the expression levels of TIMP1 and E-cadherin, whereas progesterone significantly decreased expression of MMP-9 and significantly increased levels of TIMP1, TIMP2, and E-cadherin. Leptin promotes invasion of BeWo cells, and progesterone suppresses leptin-induced invasion by regulating the expressions of MMP-9, TIMP1, TIMP2, and E-cadherin. The balance between leptin and progesterone may play an important role in human placenta formation during early pregnancy.

Systemic progesterone for modulating electrocautery-induced secondary brain injury.

PubMed

Un, Ka Chun; Wang, Yue Chun; Wu, Wutian; Leung, Gilberto Ka Kit

2013-09-01

Bipolar electrocautery is an effective and commonly used haemostatic technique but it may also cause iatrogenic brain trauma due to thermal injury and secondary inflammatory reactions. Progesterone has anti-inflammatory and neuroprotective actions in traumatic brain injury. However, its potential use in preventing iatrogenic brain trauma has not been explored. We conducted a pilot animal study to investigate the effect of systemic progesterone on brain cellular responses to electrocautery-induced injury. Adult male Sprague-Dawley rats received standardized bipolar electrocautery (40 W for 2 seconds) over the right cerebral cortex. The treatment group received progesterone intraperitoneally 2 hours prior to surgery; the control group received the drug vehicle only. Immunohistochemical studies showed that progesterone could significantly reduce astrocytic hypertrophy on postoperative day 1, 3 and 7, as well as macrophage infiltration on day 3. The number of astrocytes, however, was unaffected. Our findings suggest that progesterone should be further explored as a neuroprotective agent against electrocautery-induced or other forms of iatrogenic trauma during routine neurosurgical procedures. Future studies may focus on different dosing regimens, neuronal survival, functional outcome, and to compare progesterone with other agents such as dexamethasone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of the dye stain assay and ultraviolet light test for assessing vaginal insertion of placebo-filled applicators before and after sex.

PubMed

Keller, Marla J; Buckley, Niall; Katzen, Lauren L; Walsh, Jennifer; Friedland, Barbara; Littlefield, Sarah; Lin, Juan; Xue, Xiaonan; Cornelison, Terri; Herold, Betsy C; Einstein, Mark H

2013-12-01

Applicator dye staining and ultraviolet (UV) light have been used in trials to measure adherence, but not in the setting of before and after sex gel dosing (BAT-24). This study was designed to determine if semen or presex gel dosing impacts the sensitivity and specificity of a dye stain assay (DSA) for measuring vaginal insertion of placebo-filled applicators with BAT-24 dosing. Healthy monogamous couples received Microlax-type applicators (Tectubes, Åstorp, Sweden) filled with hydroxyethylcelluose placebo gel. Women were instructed to vaginally insert 1 dose of gel before and a second dose after sex and to return applicators within 48 hours after sex. Applicators were stained to detect semen, followed by UV then DSA, and scored by 2 readers. Positive and negative controls were randomly included in applicator batches. Fifteen couples completed the study. Each woman returned at least 6 applicators over a 30-day period. The sensitivity for insertion of postsex applicators was higher for UV (97%) compared with DSA (90%), and the specificity was similar (≥96%). For presex applicators, the sensitivity and specificity were higher for DSA (100%) compared with UV testing (87% sensitivity, 96% specificity). Among returned postsex applicators, 95% tested positive by UV compared with 87% by DSA. Agreement between readers was significantly better on the presex applicators for DSA than for UV, and for postsex readings, agreement was less than half that for UV, although the results were not statistically significant. Applicator tests are feasible for measuring adherence in trials with gel dosing before and after sex.

Progesterone, prolactin, and gynaecomastia in men with liver disease.

PubMed Central

Farthing, M J; Green, J R; Edwards, C R; Dawson, A M

1982-01-01

Plasma progesterone was raised in 36 of 50 (72%) men with liver disease compared with 20 healthy male control subjects. Plasma progesterone was significantly higher in men with non-alcoholic cirrhosis with gynaecomastia than those without, but no similar relationship was found in men with alcoholic fatty change and alcoholic cirrhosis. Hyperprolactinaemia was found in 14% of men with liver disease but levels were unrelated to the presence of gynaecomastia. Increased circulating levels of progesterone and prolactin alone do not explain the development of gynaecomastia in patients with liver disease, but progesterone may be an additional factor acting in association with the known disturbances of other sex steroids. PMID:7076004

Self-emulsifying drug delivery systems: Design of a novel vaginal delivery system for curcumin.

PubMed

Köllner, S; Nardin, I; Markt, R; Griesser, J; Prüfert, F; Bernkop-Schnürch, A

2017-06-01

The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization. The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS. Additionally to mucus binding studies, permeation studies in the mucus were performed. Furthermore, spreading potential of the novel developed formulations was compared with a commercial available o/w cream (non-ionic hydrophilic cream) on vaginal mucosa. SEDDS displayed a mean droplet size between 38 and 141nm and a zeta potential of -0.3 to -1.6mV. The collagen swelling test indicated no significant irritation potential of both formulations over 24h. An immediate interaction of unformulated curcumin with the mucus was determined, whereas both SEDDS facilitated drug permeation through the mucus layer. Formulation B showed a 2.2-fold improved transport ratio of curcumin compared to SEDD formulation A. In comparison to the vaginal cream, SEDD formulation A and B were able to spread over the vaginal mucosa and cover the tissue to a 17.8- and 14.8-fold higher extent, respectively. According to these results, SEDDS seems to be a promising tool for vaginal application. Copyright © 2017 Elsevier B.V. All rights reserved.

Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?

PubMed

Miller, Elizabeth A; Beasley, DeAnna E; Dunn, Robert R; Archie, Elizabeth A

2016-01-01

The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus , which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies ( N = 21 mammals for pH and 14 mammals for lactobacilli relative abundance). We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4-7.8). Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli relative abundance and multiple metrics of STD or birth injury risk ( P -values ranged from 0.13 to 0.99). Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non

DORSAL HIPPOCAMPAL PROGESTERONE INFUSIONS ENHANCE OBJECT RECOGNITION IN YOUNG FEMALE MICE

PubMed Central

Orr, Patrick T.; Lewis, Michael C.; Frick, Karyn M.

2009-01-01

The effects of progesterone on memory are not nearly as well studied as the effects of estrogens. Although progesterone can reportedly enhance spatial and/or object recognition in female rodents when given immediately after training, previous studies have injected progesterone systemically, and therefore, the brain regions mediating this enhancement are not clear. As such, this study was designed to determine the role of the dorsal hippocampus in mediating the beneficial effect of progesterone on object recognition. Young ovariectomized C57BL/6 mice were trained in a hippocampal-dependent object recognition task utilizing two identical objects, and then immediately or 2 hrs afterwards, received bilateral dorsal hippocampal infusions of vehicle or 0.01, 0.1, or 1.0 μg/μl water-soluble progesterone. Forty-eight hours later, object recognition memory was tested using a previously explored object and a novel object. Relative to the vehicle group, memory for the familiar object was enhanced in all groups receiving immediate infusions of progesterone. Progesterone infusion delayed 2 hrs after training did not affect object recognition. These data suggest that the dorsal hippocampus may play a critical role in progesterone-induced enhancement of object recognition. PMID:19477194

Clothing factors and vaginitis.

PubMed

Heidrich, F E; Berg, A O; Bergman, J J

1984-10-01

Associations of clothing factors and vulvovaginal symptoms, signs, and microbiology were sought in 203 women seeking care at a university family medicine clinic. Clothing factors studied were use of panty hose, underwear for sleep, cotton lining panels, and pants vs skirts. Women wearing and not wearing panty hose had similar rates of vaginitis symptoms and signs, but yeast vaginitis was about three times more common among wearers. Relationships of other clothing factors to vaginitis were not found. Nonspecific vaginitis was not found to be related to clothing.

Progesterone receptors in the female lower urinary tract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batra, S.C.; Iosif, C.S.

1987-11-01

When female estrogenized rabbits were injected i.v. with /sup 3/H-progesterone, the tritium concentration determined after one hour was about two to three times higher in urethra, urinary bladder and vagina than in the heart. High affinity progesterone receptors (KD = 1-2 nM) could be demonstrated in both cytoplasmic and nuclear fractions prepared from estrogenized rabbit urethra, bladder and vagina. The cytosolic receptor concentration in both urethra and bladder was about half of that in the vagina. The concentration of nuclear receptors in urethra was not significantly different from that in the vagina, but in the bladder the concentration was onlymore » about one fourth of that in the vagina or urethra. The mean KD of cytosolic receptors from bladder was significantly higher than the corresponding values in urethra and vagina. Progesterone binding sites in the bladder had a broader hormonal specificity than those in the urethra or vagina. The present demonstration of specific progesterone receptors in the female urethra might provide a possible link between estrogen progesterone interaction and the appearance of urinary incontinence during pregnancy in women.« less

The concentration-dependent effect of progesterone on follicle growth in the mouse ovary.

PubMed

Komatsu, Kouji; Masubuchi, Satoru

2017-06-21

Follicle growth in the mammalian ovary is coordinately controlled by multiple factors to sustain periodic ovulation. In this study, we investigated the role of progesterone on follicle growth in the mouse ovary. As the concentration of progesterone changes during the estrus cycle, we cultured the sliced mouse ovary in a medium containing 10 ng/ml, 100 ng/ml, and 1 μg/ml progesterone. Progesterone promoted the growth of primordial to primary follicles at 100 ng/ml, while it suppressed the growth of secondary follicles at 1 μg/ml. Follicles at other developmental stages in the cultured ovary were unaffected with different concentrations of progesterone. The number of ovulated oocytes increased in the medium containing 100 ng/ml progesterone but decreased in the presence of 1 μg/ml progesterone. Follicles expressed two types of progesterone receptors, progesterone receptor (PGR) and PGR membrane component 1 (PGRMC1). While PGR shows transient expression on granulosa cells of Graafian follicles, PGRMC1 expresses in granulosa cells of developing follicles. These results suggest that progesterone controls the growth of developing follicles through PGRMC1. Our study shows that the effect of progesterone on ovulation and follicle growth in mouse ovary is dependent on the concentration of progesterone and the follicle stage.

A randomized comparison of the efficacy, side effects and patient convenience between vaginal and rectal administration of Cyclogest(®) when used for luteal phase support in ICSI treatment.

PubMed

Aghsa, Malek-Mansour; Rahmanpour, Haleh; Bagheri, Maryam; Davari-Tanha, Fatemeh; Nasr, Reza

2012-10-01

This study compares the efficacy, side effects and patient convenience of vaginal and rectal routes of administration of progesterone suppositories (Cyclogest) when used for luteal phase support during in vitro fertilization cycles, through the use of antagonist protocols. 147 patients who underwent intra-cytoplasmic sperm injection cycle were randomized on the day of the embryo transfer (ET) by a computer-generated randomization program to receive 400 mg of Cyclogest either vaginally or rectally twice daily for up to 8 weeks. A pregnancy test was conducted 2 weeks after embryo transfer. If the pregnancy test was negative, the application was discontinued. On day 14th after embryo transfer, patient's acceptability and side effects were assessed using a questionnaire which was given to the patients on the day of ET prior to performing the pregnancy test. The clinical pregnancy rate at the 8th week of gestation and the level of luteal progesterone were evaluated. There were no substantial differences in the demographics or other characteristics between the two groups. There were no significant differences in serum P concentration 6 days after ET, the clinical pregnancy and abortion rates. The difficulty of administration route, the discomforts experienced following administration, and the proportion leaking out on the 14th day were similar between the two groups. Significantly more patients administering the medication per vagina had perineal irritation (21.3 vs. 2.2 %). The prevalence of tenesmus (35.1 vs. 21.1 %) and rectal itching (26.7 vs. 2.8 %) were significantly more in rectal route. This study demonstrates that the efficacy of Cyclogest is similar when administered via both the vaginal and rectal routes. Although their side effects differ, the ease of administration for patients and their preference are similar.

Effect of vaginal or systemic estrogen on dynamics of collagen assembly in the rat vaginal wall.

PubMed

Montoya, T Ignacio; Maldonado, P Antonio; Acevedo, Jesus F; Word, R Ann

2015-02-01

The objective of this study was to compare the effects of systemic and local estrogen treatment on collagen assembly and biomechanical properties of the vaginal wall. Ovariectomized nulliparous rats were treated with estradiol or conjugated equine estrogens (CEEs) either systemically, vaginal CEE, or vaginal placebo cream for 4 wk. Low-dose local CEE treatment resulted in increased vaginal epithelial thickness and significant vaginal growth without uterine hyperplasia. Furthermore, vaginal wall distensibility increased without compromise of maximal force at failure. Systemic estradiol resulted in modest increases in collagen type I with no change in collagen type III mRNA. Low-dose vaginal treatment, however, resulted in dramatic increases in both collagen subtypes whereas moderate and high dose local therapies were less effective. Consistent with the mRNA results, low-dose vaginal estrogen resulted in increased total and cross-linked collagen content. The inverse relationship between vaginal dose and collagen expression may be explained in part by progressive downregulation of estrogen receptor-alpha mRNA with increasing estrogen dose. We conclude that, in this menopausal rat model, local estrogen treatment increased total and cross-linked collagen content and markedly stimulated collagen mRNA expression in an inverse dose-effect relationship. High-dose vaginal estrogen resulted in downregulation of estrogen receptor-alpha and loss of estrogen-induced increases in vaginal collagen. These results may have important clinical implications regarding the use of local vaginal estrogen therapy and its role as an adjunctive treatment in women with loss of vaginal support. © 2015 by the Society for the Study of Reproduction, Inc.

Role of nuclear progesterone receptor isoforms in uterine pathophysiology

PubMed Central

Patel, Bansari; Elguero, Sonia; Thakore, Suruchi; Dahoud, Wissam; Bedaiwy, Mohamed; Mesiano, Sam

2015-01-01

BACKGROUND Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function. METHODS Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed. RESULTS Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS.

PubMed

Gupta, Satish Kumar; Nutan

2013-10-22

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

PubMed Central

Gupta, Satish Kumar; Nutan

2013-01-01

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other

Assisted Vaginal Delivery

MedlinePlus

... Patient Education FAQs Assisted Vaginal Delivery Patient Education Pamphlets - Spanish Assisted Vaginal Delivery FAQ192, February 2016 PDF ... on Patient Safety For Patients Patient FAQs Spanish Pamphlets Teen Health About ACOG About Us Leadership & Governance ...

Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall.

PubMed

Ripperda, Christopher M; Maldonado, Pedro Antonio; Acevedo, Jesus F; Keller, Patrick W; Akgul, Yucel; Shelton, John M; Word, Ruth Ann

2017-07-01

Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium. Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury.

Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall

PubMed Central

Ripperda, Christopher M.; Maldonado, Pedro Antonio; Acevedo, Jesus F.; Keller, Patrick W.; Akgul, Yucel; Shelton, John M.; Word, Ruth Ann

2017-01-01

Abstract Objective: Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Methods: Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). Results: MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium. Conclusions: Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury. PMID:28169915

Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection

PubMed Central

Abdool Karim, Salim S.; Karim, Quarraisha Abdool; Kharsany, Ayesha B.M.; Baxter, Cheryl; Grobler, Anneke C.; Werner, Lise; Kashuba, Angela; Mansoor, Leila E.; Samsunder, Natasha; Mindel, Adrian; Gengiah, Tanuja N.

2015-01-01

BACKGROUND Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P = 0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P = 0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P = 0.005). CONCLUSIONS In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.) PMID:26244306

Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?

PubMed Central

Miller, Elizabeth A.; Beasley, DeAnna E.; Dunn, Robert R.; Archie, Elizabeth A.

2016-01-01

The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus, which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies (N = 21 mammals for pH and 14 mammals for lactobacilli relative abundance). We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4–7.8). Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli relative abundance and multiple metrics of STD or birth injury risk (P-values ranged from 0.13 to 0.99). Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non

Disturbances in production of progesterone and their implications in plant studies.

PubMed

Janeczko, Anna; Oklestkova, Jana; Novak, Ondrej; Śniegowska-Świerk, Katarzyna; Snaczke, Zuzanna; Pociecha, Ewa

2015-04-01

Progesterone is a mammalian hormone that has also been discovered in plants but its physiological function in plants is not explained. Experiments using inhibitors of progesterone synthesis and binding would be useful in studies on the significance of this compound in plants. Until now, trilostane and mifepristone have been used in medical sciences as progesterone biosynthesis and binding inhibitors, respectively. We tested these synthetic steroids for the first time in plants and found that they reduced the content of progesterone in wheat. The aim of further experiments was to answer whether the potential disturbances in the production/binding of progesterone, influence resistance to environmental stress (drought) and the development of wheat. Inhibitors and progesterone were applied to plants via roots in a concentration of 0.25-0.5mg/l water. Both inhibitors lowered the activity of CO2 binding enzyme (Rubisco) in wheat exposed to drought stress and trilostane additionally lowered the chlorophyll content. However, trilostane-treated plants were rescued by treatment with exogenous progesterone. The inhibitors also modulated the development of winter wheat, which indicated the significance of steroid regulators and their receptors in this process. In this study, in addition to progesterone and its inhibitors, brassinosteroid (24-epibrassinolide) and an inhibitor of biosynthesis of brassinosteroids were also applied. Mifepristone inhibited the generative development of wheat (like 24-epibrassinolide), while trilostane (like progesterone and an inhibitor of biosynthesis of brassinosteroids) stimulated the development. We propose a model of steroid-induced regulation of the development of winter wheat, where brassinosteroids act as inhibitors of generative development, while progesterone or other pregnane derivatives act as stimulators. Copyright © 2015 Elsevier Inc. All rights reserved.

Progesterone from maternal circulation binds to progestin receptors in fetal brain.

PubMed

Wagner, Christine K; Quadros-Mennella, Princy

2017-06-01

Steroid hormones activate nuclear receptors which, as transcription factors, can regulate critical aspects of neural development. Many regions of the rat forebrain, midbrain and hindbrain express progestin receptors (PR) during perinatal life, suggesting that progesterone may play an important role in the development of the brain. An immunohistochemical approach using two antibodies with differential recognition of ligand-bound PR was used to examine whether fetuses are exposed to maternal progesterone during pregnancy and whether progesterone from maternal circulation can bind to PR within the fetal brain. Findings demonstrate that maternal and fetal serum progesterone levels are positively correlated at the end of gestation, suggesting a common source of progesterone in mothers and fetuses (e.g., the maternal ovary). Additional findings suggest that administration of exogenous progesterone to mothers not only increases fetal serum progesterone levels within 2 h, but appears to increase ligand-bound PR in fetal brain. These findings suggest that progesterone of maternal origin may play a previously overlooked role in neural development. In addition, there are implications for the ongoing prophylactic use of synthetic progestins in pregnant women for the prevention of premature birth. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 767-774, 2017. © 2016 Wiley Periodicals, Inc.

Progesterone regulation of primordial follicle assembly in bovine fetal ovaries.

PubMed

Nilsson, Eric E; Skinner, Michael K

2009-12-10

Fertility in mammals is dependant on females having an adequate primordial follicle pool to supply oocytes for fertilization. The formation of primordial follicles is called ovarian follicular assembly. In rats and mice progesterone and estradiol have been shown to inhibit follicle assembly with assembly occurring after birth when the pups are removed from the high-steroid maternal environment. In contrast, primordial follicle assembly in other species, such as cattle and humans, occurs during fetal development before birth. The objective of the current study is to determine if progesterone levels regulate primordial follicle assembly in fetal bovine ovaries. Ovaries and blood were collected from bovine fetuses. Interestingly, ovarian progesterone and estradiol concentrations were found to decrease with increasing fetal age and correlated to increased primordial follicle assembly. Microarray analysis of fetal ovary RNA suggests that progesterone membrane receptor and estrogen nuclear receptor are expressed. Treatment of fetal bovine ovary cultures with a higher progesterone concentration significantly decreased primordial follicle assembly. Observations indicate that progesterone affects ovarian primordial follicle assembly in cattle, as it does in rats and mice.

Progesterone Regulation of Primordial Follicle Assembly In Bovine Fetal Ovaries

PubMed Central

Nilsson, Eric E.; Skinner, Michael K.

2009-01-01

Fertility in mammals is dependant on females having an adequate primordial follicle pool to supply oocytes for fertilization. The formation of primordial follicles is called ovarian follicular assembly. In rats and mice progesterone and estradiol have been shown to inhibit follicle assembly with assembly occurring after birth when the pups are removed from the high-steroid maternal environment. In contrast, primordial follicle assembly in other species, such as cattle and humans, occurs during fetal development before birth. The objective of the current study is to determine if progesterone levels regulate primordial follicle assembly in fetal bovine ovaries. Ovaries and blood were collected from bovine fetuses. Interestingly, ovarian progesterone and estradiol concentrations were found to decrease with increasing fetal age and correlated to increased primordial follicle assembly. Microarray analysis of fetal ovary RNA suggests that progesterone membrane receptor and estrogen nuclear receptor are expressed. Treatment of fetal bovine ovary cultures with a higher progesterone concentration significantly decreased primordial follicle assembly. Observations indicate that progesterone affects ovarian primordial follicle assembly in cattle, as it does in rats and mice. PMID:19747959

The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production.

PubMed

Akgul, Yucel; Derk, Raymond C; Meighan, Terence; Rao, K Murali Krishna; Murono, Eisuke P

2011-07-01

The methoxychlor metabolite, HPTE, was shown to inhibit P450-cholesterol side-chain cleavage (P450scc) activity resulting in decreased progesterone production by cultured ovarian follicular cells in previous studies. It is not known whether HPTE has any effect on progesterone formation by the corpus luteum. Exposure to 100 nM HPTE reduced progesterone production by luteal cells with progressive declines to <22% of control at 500 nM HPTE. Similarly, HPTE progressively inhibited progesterone formation and P450scc catalytic activity of hCG- or 8 Br-cAMP-stimulated luteal cells. However, HPTE did not alter mRNA and protein levels of P450scc. Compounds acting as estrogen (17 β-estradiol, bisphenol-A or octylphenol), antiestrogen (ICI) or antiandrogen (monobutyl phthalate, flutamide or M-2) added alone to luteal cells did not mimic the action of HPTE on progesterone and P450scc activity. These results suggest that HPTE directly inhibits P450scc catalytic activity resulting in reduced progesterone formation, and this action was not mediated through estrogen or androgen receptors. Published by Elsevier Inc.

Randomized clinical trial comparing the efficacy of the vaginal use of metronidazole with a Brazilian pepper tree (Schinus) extract for the treatment of bacterial vaginosis.

PubMed

Leite, S R R F; Amorim, M M R; Sereno, P F B; Leite, T N F; Ferreira, J A C; Ximenes, R A A

2011-03-01

A 7.4% vaginal extract of the Brazilian pepper tree (Schinus terebinthifolius Raddi) was compared with 0.75% vaginal metronidazole, both manufactured by the Hebron Laboratory, for the treatment of bacterial vaginosis, used at bedtime for 7 nights. The condition was diagnosed using the combined criteria of Amsel and Nugent in two groups of 140 and 137 women, aged between 18 and 40 years. Intention-to-treat analysis was performed. Women were excluded from the study if they presented delayed menstruation, were pregnant, were using or had used any topical or systemic medication, presented any other vaginal infections, presented hymen integrity, or if they reported any history suggestive of acute pelvic inflammatory disease. According to Amsel's criteria separately, 29 patients (21.2%) treated with the extract and 87 (62.1%) treated with metronidazole were considered to be cured (P < 0.001). According to Nugent's score separately, 19 women (13.9%) treated with the extract and 79 (56.4%) treated with metronidazole were considered to be cured (P < 0.001). Using the two criteria together, the so-called total cure was observed in 17 women (12.4%) treated with the extract and in 79 women (56.4%) treated with metronidazole (P < 0.001). In conclusion, the cure rate for bacterial vaginosis using a vaginal gel from a pepper tree extract was lower than the rate obtained with metronidazole gel, while side effects were infrequent and non-severe in both groups.

Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women.

PubMed

Westhoff, Carolyn L; Torgal, Anupama H; Mayeda, Elizabeth Rose; Petrie, Kelsey; Thomas, Tiffany; Dragoman, Monica; Cremers, Serge

2012-07-01

Many observational studies indicate higher oral contraceptive failure among obese women, but most clinical trials and physiologic studies do not support these differences. Limited data indicate higher failure rates among obese contraceptive patch users. Data regarding contraceptive vaginal ring performance in obese women are needed. Twenty normal weight (body mass index [BMI] 19.0-24.9; median, 21.65) and 20 obese (BMI 30.0-39.9; median, 33.7) women enrolled in a prospective study of ethinyl estradiol (EE(2)) and etonorgestrel pharmacokinetics and of ovarian follicle development, endometrial thickness, and bleeding patterns, all measured biweekly during the second cycle of contraceptive vaginal ring use. Thirty-seven women completed follow-up. Mean day 0-21 EE(2) concentrations were lower among obese vs normal weight women (15.0 vs 22.0 pg/mL, respectively, P = .004), whereas etonorgestrel concentrations were similar (1138 vs 1256 pg/mL, respectively, P = .39). Follicular development was minimal in both groups, with only 5 women achieving a maximum follicle diameter >13 mm at any time during 3 weeks follow-up (3 normal weight and 2 obese women); these women had serum progesterone levels <1.0. Obese women reported more bleeding or spotting than normal weight women (3.6 vs 1.4 days, respectively, P = .01). Although obese women had lower EE(2) levels during contraceptive vaginal ring use, they had excellent suppression of ovarian follicle development, similar to normal weight women. This predicts that contraceptive vaginal ring effectiveness will be similar in women with a BMI up to 39.9. The lower serum EE(2) levels in the obese women may explain the greater reported bleeding or spotting days. Copyright © 2012 Mosby, Inc. All rights reserved.

Combined liquid chromatography-tandem mass spectrometry analysis of progesterone metabolites.

PubMed

Sinreih, Maša; Zukunft, Sven; Sosič, Izidor; Cesar, Jožko; Gobec, Stanislav; Adamski, Jerzy; Lanišnik Rižner, Tea

2015-01-01

Progesterone has a number of important functions throughout the human body. While the roles of progesterone are well known, the possible actions and implications of progesterone metabolites in different tissues remain to be determined. There is a growing body of evidence that these metabolites are not inactive, but can have significant biological effects, as anesthetics, anxiolytics and anticonvulsants. Furthermore, they can facilitate synthesis of myelin components in the peripheral nervous system, have effects on human pregnancy and onset of labour, and have a neuroprotective role. For a better understanding of the functions of progesterone metabolites, improved analytical methods are essential. We have developed a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection and quantification of progesterone and 16 progesterone metabolites that has femtomolar sensitivity and good reproducibility in a single chromatographic run. MS/MS analyses were performed in positive mode and under constant electrospray ionization conditions. To increase the sensitivity, all of the transitions were recorded using the Scheduled MRM algorithm. This LC-MS/MS method requires small sample volumes and minimal sample preparation, and there is no need for derivatization. Here, we show the application of this method for evaluation of progesterone metabolism in the HES endometrial cell line. In HES cells, the metabolism of progesterone proceeds mainly to (20S)-20-hydroxy-pregn-4-ene-3-one, (20S)-20-hydroxy-5α-pregnane-3-one and (20S)-5α-pregnane-3α,20-diol. The investigation of possible biological effects of these metabolites on the endometrium is currently undergoing.

[Interest of selective progesterone receptor modulators in endometriosis].

PubMed

Merviel, P; Lourdel, E; Sanguin, S; Gagneur, O; Cabry, R; Nasreddine, A

2013-09-01

The SPRM (selective progesterone receptor modulators) are agonists and/or antagonists of progesterone receptor. They are responsible for anovulation, amenorrhea and a lower prostaglandin levels, which leads to an improvement in pain and regression of lesions in endometriosis. On the endometrium, a particular aspect, the progesterone receptor modulator-associated endometrial changes (PAEC), raises additional studies to verify its harmlessness. However, due to the lack of hypoestrogenism and metabolic effects with these drugs, it is very likely that the SPRM will in the near future an important place in the treatment of endometriosis. Copyright © 2013. Published by Elsevier SAS.

Progesterone regulation of stem and progenitor cells in normal and malignant breast

PubMed Central

Axlund, Sunshine Daddario; Sartorius, Carol A.

2011-01-01

Progesterone plays an important, if not controversial, role in mammary epithelial cell proliferation and differentiation. Evidence supports that progesterone promotes rodent mammary carcinogenesis under some conditions, progesterone receptors (PR) are necessary for murine mammary gland tumorigenesis, and exogenous progestin use in post-menopausal women increases breast cancer risk. Thus, the progesterone/PR signaling axis can promote mammary tumorigenesis, albeit in a context dependent manner. A mechanistic basis for the tumor promoting actions of progesterone has thus far remained unknown. Recent studies, however, have identified a novel role for progesterone in controlling the number and function of stem and progenitor cell populations in the normal human and mouse mammary glands, and in human breast cancers. These discoveries promise to reshape our perception of progesterone function in the mammary gland, and have spawned new hypotheses for how progestins may increase the risk of breast cancer. Here we review studies on progesterone regulation of mammary stem cells in normal and malignant tissue, and their implications for breast cancer risk, tumorigenesis, and tumor behavior. PMID:21945473

Contrasting effects of progesterone on fertility of dairy and beef cows.

PubMed

Stevenson, J S; Lamb, G C

2016-07-01

The role of progesterone in maintaining pregnancy is well known in the bovine. Subtle differences exist between dairy and beef cows because of differing concentrations of progesterone during recrudescence of postpartum estrous cycles, rate of follicular growth and maturation, proportions of 2- and 3-follicular wave cycles, and other effects on pregnancy outcomes per artificial insemination (P/AI). Because proportions of anovulatory cows before the onset of the artificial insemination (AI) period are greater and more variable in beef (usually ranging from 30 to 70%) than dairy (25%) cows, AI programs were developed to accommodate anovulatory and cycling beef cows enrolled therein. Incorporating a progestin as part of an AI program in beef cows improved P/AI by reducing the proportion of cows having premature luteal regression and short post-AI luteal phases. In both genotypes, prolonged dominant follicle growth in a reduced progesterone milieu resulted in increased (1) LH pulses, (2) preovulatory follicle diameter, and (3) concentrations of estradiol and a subsequently larger corpora lutea (CL). In contrast, the progesterone milieu during growth of the ovulatory follicle in an ovulation control program does not seem to affect subsequent P/AI in beef cows, whereas in dairy cows follicle development in an elevated compared with a low progesterone environment increases P/AI. Progesterone status in beef cows at the onset of ovulation synchronization is not related to P/AI in multiparous cows, whereas P/AI was suppressed in primiparous cows that began a timed AI program in a low-progesterone environment. In timed AI programs, elevated concentrations of progesterone just before PGF2α and reduced concentrations at AI are critical to maximizing subsequent P/AI in dairy cows, but seemingly much less important in beef cows. By inducing ancillary CL and increasing concentrations of progesterone, human chorionic gonadotropin may increase P/AI when administered to beef cows 7d

Dinoprostone vaginal insert versus intravenous oxytocin to reduce postpartum blood loss following vaginal or cesarean delivery.

PubMed

Ozalp, E; Tanir, H M; Sener, T

2010-01-01

To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery. This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section. In the vaginally delivered cases, active management of the third stage of labor was conducted. During cesarean delivery, 20 IU of intravenous oxytocin was administered. Women, who either delivered via the vaginal or abdominal route, were then randomly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours (group I, n: 100) or intravenous oxytocin (group II, n: 100), respectively. Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups. Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting. Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss.

Evaluation of vaginal complaints.

PubMed

Anderson, Matthew R; Klink, Kathleen; Cohrssen, Andreas

2004-03-17

Vaginal symptoms are one of the most common reasons for gynecological consultation. Clinicians have traditionally diagnosed vaginal candidiasis, bacterial vaginosis, and vaginal trichomoniasis using some combination of physical examination, pH, the wet mount, and the whiff test. To evaluate the role of the clinical examination and determine the positive and negative likelihood ratios (LRs) for the diagnosis of vaginal candidiasis, bacterial vaginosis, and vaginal trichomoniasis. Using a structured literature review, we abstracted information on sensitivity and specificity for symptoms, signs, and office laboratory procedures. We chose published (1966 to April 2003) articles that appeared in the MEDLINE database and were indexed under the combined search terms of diagnosis with vaginitis, vaginal discharge, candidiasis, bacterial vaginosis, and trichomoniasis. Included studies of symptomatic premenopausal women seen in primary care settings. Tests were evaluated only if they would provide diagnostic information during the office visit and were compared with an acceptable criterion standard. All 3 authors extracted the data and computed sensitivity and specificity from each article independently. The absence of standard definitions for symptoms and signs made it impossible to combine results across studies. Symptoms alone do not allow clinicians to distinguish confidently between the causes of vaginitis. However, a patient's lack of itching makes candidiasis less likely (range of LRs, 0.18 [95% confidence interval [CI], 0.05-0.70] to 0.79 [95% CI, 0.72-0.87]) and lack of perceived odor makes bacterial vaginosis unlikely (LR, 0.07 [95% CI, 0.01-0.51]). Similarly, physical examination signs are limited in their diagnostic power. The presence of inflammatory signs is associated with candidiasis (range of LRs, 2.1 [95% CI, 1.5-2.8] to 8.4 [95% CI, 2.3-31]). Presence of a "high cheese" odor on examination is predictive of bacterial vaginosis (LR, 3.2 [95% CI, 2

Progesterone lipid nanoparticles: Scaling up and in vivo human study.

PubMed

Esposito, Elisabetta; Sguizzato, Maddalena; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Nastruzzi, Claudio; Cortesi, Rita

2017-10-01

This investigation describes a scaling up study aimed at producing progesterone containing nanoparticles in a pilot scale. Particularly hot homogenization techniques based on ultrasound homogenization or high pressure homogenization have been employed to produce lipid nanoparticles constituted of tristearin or tristearin in association with caprylic-capric triglyceride. It was found that the high pressure homogenization method enabled to obtain nanoparticles without agglomerates and smaller mean diameters with respect to ultrasound homogenization method. X-ray characterization suggested a lamellar structural organization of both type of nanoparticles. Progesterone encapsulation efficiency was almost 100% in the case of high pressure homogenization method. Shelf life study indicated a double fold stability of progesterone when encapsulated in nanoparticles produced by the high pressure homogenization method. Dialysis and Franz cell methods were performed to mimic subcutaneous and skin administration. Nanoparticles constituted of tristearin in mixture with caprylic/capric triglyceride display a slower release of progesterone with respect to nanoparticles constituted of pure tristearin. Franz cell evidenced a higher progesterone skin uptake in the case of pure tristearin nanoparticles. A human in vivo study, based on tape stripping, was conducted to investigate the performance of nanoparticles as progesterone skin delivery systems. Tape stripping results indicated a decrease of progesterone concentration in stratum corneum within six hours, suggesting an interaction between nanoparticle material and skin lipids. Copyright © 2017 Elsevier B.V. All rights reserved.

Steroidogenesis in plants--Biosynthesis and conversions of progesterone and other pregnane derivatives.

PubMed

Lindemann, Peter

2015-11-01

In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17β-estradiol, androsterone, testosterone or progesterone were summarized as sex hormones. These steroids influence plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. First reports on the effect of applicated substances and of their endogenous occurrence date from the early twenties of the last century. This caused later on doubts on the identity of the compounds. Best investigated is the effect of progesterone. Main steps of the progesterone biosynthetic pathway have been analyzed in Digitalis. Cholesterol-side-chain-cleavage, pregnenolone and progesterone formation as well as the stereospecific reduction of progesterone are described and the corresponding enzymes are presented. Biosynthesis of androstanes, estranes and corticoids is discussed. Possible progesterone receptors and physiological reactions on progesterone application are reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Management of vaginal extrusion after tension-free vaginal tape procedure for urodynamic stress incontinence.

PubMed

Giri, Subhasis K; Sil, Debasri; Narasimhulu, Girish; Flood, Hugh D; Skehan, Mark; Drumm, John

2007-06-01

To report our experience in the management of vaginal extrusion after the tension-free vaginal tape (TVT) procedure for urodynamic stress incontinence. Five patients diagnosed with vaginal extrusion after a TVT procedure performed at our institution were identified. We reviewed the patients' records retrospectively. The interval from TVT placement to diagnosis, presenting symptoms and signs, duration of symptoms, diagnostic test findings, treatment, and postoperative results were recorded. Patients were followed up for at least 12 months. From January 2001 to June 2004, a total of 166 patients underwent the TVT procedure. Of these, 5 patients (3%) were diagnosed with isolated vaginal extrusion 4 to 40 months postoperatively. No cases of urethral or bladder erosion occurred in this series. The symptoms included vaginal discharge, pain, bleeding, and dyspareunia. The eroded margin of the vaginal mucosa was trimmed, mobilized, and closed over the tape with interrupted vertical mattress sutures in a single layer using 2-0 polyglactin 910 to avoid mucosal inversion. All patients remained symptom free without any evidence of defective healing or additional extrusion at a minimal follow-up of 12 months. Primary reclosure of the vaginal mucosa over the TVT tape is an effective first-line treatment option for vaginal extrusion without compromising continence. Patients undergoing the TVT procedure should be adequately counseled about the possibility of this complication and the available treatment options.

Biomarkers and biometric measures of adherence to use of ARV-based vaginal rings.

PubMed

Stalter, Randy M; Moench, Thomas R; MacQueen, Kathleen M; Tolley, Elizabeth E; Owen, Derek H

2016-01-01

Poor adherence to product use has been observed in recent trials of antiretroviral (ARV)-based oral and vaginal gel HIV prevention products, resulting in an inability to determine product efficacy. The delivery of microbicides through vaginal rings is widely perceived as a way to achieve better adherence but vaginal rings do not eliminate the adherence challenges exhibited in clinical trials. Improved objective measures of adherence are needed as new ARV-based vaginal ring products enter the clinical trial stage. To identify technologies that have potential future application for vaginal ring adherence measurement, a comprehensive literature search was conducted that covered a number of biomedical and public health databases, including PubMed, Embase, POPLINE and the Web of Science. Published patents and patent applications were also searched. Technical experts were also consulted to gather more information and help evaluate identified technologies. Approaches were evaluated as to feasibility of development and clinical trial implementation, cost and technical strength. Numerous approaches were identified through our landscape analysis and classified as either point measures or cumulative measures of vaginal ring adherence. Point measurements are those that give a measure of adherence at a particular point in time. Cumulative measures attempt to measure ring adherence over a period of time. Approaches that require modifications to an existing ring product are at a significant disadvantage, as this will likely introduce additional regulatory barriers to the development process and increase manufacturing costs. From the point of view of clinical trial implementation, desirable attributes would be high acceptance by trial participants, and little or no additional time or training requirements on the part of participants or clinic staff. We have identified four promising approaches as being high priority for further development based on the following measurements

Vaginitis: current microbiologic and clinical concepts.

PubMed Central

Hill, L V; Embil, J A

1986-01-01

Infectious vaginitis occurs when the normal vaginal flora is disrupted; it may arise when saprophytes overwhelm the host immune response, when pathogenic organisms are introduced into the vagina or when changes in substrate allow an imbalance of microorganisms to develop. Examples of these types of vaginitis include the presence of chronic fungal infection in women with an inadequate cellular immune response to the yeast, the introduction of trichomonads into vaginal epithelium that has a sufficient supply of glycogen, and the alteration in bacterial flora, normally dominated by Lactobacillus spp., and its metabolites that is characteristic of "nonspecific vaginitis". The authors review microbiologic and clinical aspects of the fungal, protozoal and bacterial infections, including the interactions of bacteria thought to produce nonspecific vaginitis, that are now recognized as causing vaginitis. Other causes of vaginitis are also discussed. PMID:3510698

Vaginitis: current microbiologic and clinical concepts.

PubMed

Hill, L V; Embil, J A

1986-02-15

Infectious vaginitis occurs when the normal vaginal flora is disrupted; it may arise when saprophytes overwhelm the host immune response, when pathogenic organisms are introduced into the vagina or when changes in substrate allow an imbalance of microorganisms to develop. Examples of these types of vaginitis include the presence of chronic fungal infection in women with an inadequate cellular immune response to the yeast, the introduction of trichomonads into vaginal epithelium that has a sufficient supply of glycogen, and the alteration in bacterial flora, normally dominated by Lactobacillus spp., and its metabolites that is characteristic of "nonspecific vaginitis". The authors review microbiologic and clinical aspects of the fungal, protozoal and bacterial infections, including the interactions of bacteria thought to produce nonspecific vaginitis, that are now recognized as causing vaginitis. Other causes of vaginitis are also discussed.

Effect of Vaginal or Systemic Estrogen on Dynamics of Collagen Assembly in the Rat Vaginal Wall1

PubMed Central

Montoya, T. Ignacio; Maldonado, P. Antonio; Acevedo, Jesus F.; Word, R. Ann

2014-01-01

ABSTRACT The objective of this study was to compare the effects of systemic and local estrogen treatment on collagen assembly and biomechanical properties of the vaginal wall. Ovariectomized nulliparous rats were treated with estradiol or conjugated equine estrogens (CEEs) either systemically, vaginal CEE, or vaginal placebo cream for 4 wk. Low-dose local CEE treatment resulted in increased vaginal epithelial thickness and significant vaginal growth without uterine hyperplasia. Furthermore, vaginal wall distensibility increased without compromise of maximal force at failure. Systemic estradiol resulted in modest increases in collagen type I with no change in collagen type III mRNA. Low-dose vaginal treatment, however, resulted in dramatic increases in both collagen subtypes whereas moderate and high dose local therapies were less effective. Consistent with the mRNA results, low-dose vaginal estrogen resulted in increased total and cross-linked collagen content. The inverse relationship between vaginal dose and collagen expression may be explained in part by progressive downregulation of estrogen receptor-alpha mRNA with increasing estrogen dose. We conclude that, in this menopausal rat model, local estrogen treatment increased total and cross-linked collagen content and markedly stimulated collagen mRNA expression in an inverse dose-effect relationship. High-dose vaginal estrogen resulted in downregulation of estrogen receptor-alpha and loss of estrogen-induced increases in vaginal collagen. These results may have important clinical implications regarding the use of local vaginal estrogen therapy and its role as an adjunctive treatment in women with loss of vaginal support. PMID:25537371