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Recurrent genital candidosis in women and the effect of intermittent prophylactic treatment.

A study of clotrimazole for the treatment of recurrent genital candidosis unexpectedly showed that symptoms and infection can be dissociated. The aim of the study was to see if intermittent antifungal treatment would reduce symptoms in women constantly distressed by recurrent genital candidosis. Forty women seriously affected by the condition were initially given oral and local antifungal treatment. When the patients were symptom-free and the vagina was free of yeasts, they were entered into a double-blind clinical trial and were treated prophylactically for four months with either intermittent clotrimazole pessaries and cream or a placebo. The prophylactic treatment kept symptoms below a critical level but did not affect the return of the yeasts to the vagina. This dissociation between symptoms and vaginal yeasts was unexpected. Rectal yeast carriage was unaffected by prophylactic vaginal treatment. Male contacts and patients both showed a high incidence of non-specific genital infection. This association has seldom been reported. A few patients cultured yeasts from their homes but this environment was not considered a major source of reinfection. The vaginal pH did not appear to be altered by the presence of yeasts. The results of the study suggested that symptoms in women with recurrent genital candidosis were not caused by yeasts alone, and possibly the reason for recurrences might lie not in constant reinfection by yeasts, but in failure to recognise and remove a primary underlying factor, perhaps infection with other sexually transmitted agents. The question of a synergistic action between yeasts and other organisms is discussed.

Adult↗

Current approaches to the diagnosis, treatment, and reporting of trichomoniasis and candidosis.

The current approach to the management of trichomoniasis and candidosis in sexually transmitted disease (STD) clinics in England and Wales is described. Microscopy alone was used in the diagnosis of trichomoniasis in 44% of clinics and of candidosis in 35% of clinics. Oral metronidazole was used for the treatment of trichomoniasis in women in 92% of clinics. Vaginal pessaries containing nystatin or clotrimazole were routinely used to treat candidosis in 95% of clinics. Male sexual contacts of female patients with candidosis and trichomoniasis were invited to attend for examination in 88% of clinics. Physicians in 81% of clinics prescribed treatment on epidemiological grounds for male contacts of female patients with trichomoniasis. A more uniform approach to the diagnostic categories used for the quarterly returns for cases treated epidemiologically is recommended.

Candidiasis, Vulvovaginal↗

Vaginal pH and microflora related to yeast infections and treatment.

The relationship between vaginal pH, microflora, and yeast infection was investigated in 93 women randomly treated with either nystatin or miconazole pessaries and cream for two weeks. The vaginal pH was measured in a control group of 48 women. In the study group, 37 patients defaulted, 39 were cured, and 17 required treatment during the six-month follow-up period. In both study and control groups before and after treatment the mean vaginal pH was in the range of 4.3-4.6. Lactobacilli were plentiful in 78 (91%) out of 86 patients and shows that lactobacilli and yeasts commonly coexist. The influence of other organisms appeared to be negligible. The trial showed that nystatin and micromazole were equallly effective in the treatment of vaginal yeast infection and that the broad-spectrum activity of micronazole offered no advantage in this condition.

Adolescent↗

Aetiology and management of non-specific vaginitis.

In a study of 100 women with non-specific vaginitis, characterised by a vaginal discharge which was malodorous and pruritic in most cases and caused dyspareunia and dysuria in some, Gardnerella vaginalis was isolated in 46% of patients. When present, G vaginalis was significantly associated with Mycoplasma hominis and Bacteroides species. Isolation of G vaginalis was unrelated to the presenting symptoms. Treatment with povidone-iodine pessaries for two weeks produced no pronounced benefit, either clinically or microbiologically, compared with a placebo. Nevertheless, 68% of all patients followed reported improvement four weeks after the start of treatment. The findings suggest that G vaginalis is one cause of non-specific vaginitis, which is more likely to be seen in women using oral contraceptives and is usually cured spontaneously.

Adolescent↗

An investigation into the pathogenesis of vulvo-vaginal candidosis.

OBJECTIVE: To monitor yeasts isolated from women during and between episodes of recurrent vulvo-vaginal candidosis (VVC) to determine whether vaginal relapse or re-infection occurred. METHODS: Women presenting at the genitourinary medicine clinic with signs and symptoms of VVC were recruited to the study (n = 121). A vaginal washing, high vaginal swab (HVS) and rectal swab were taken and the women treated with a single 500 mg clotrimazole pessary. Women were asked to re-attend after 1, 4, and 12 weeks, or when the VVC recurred, when vaginal washings and HVS were repeated. Candida isolates recovered were strain typed using the Ca3 probe and their similarity assessed. Antifungal susceptibility to fluconazole and clotrimazole were determined. RESULTS: Of the women recruited, 47 completed the study, either returning for four visits or suffering a recurrence during the study period. Of the 22 women who experienced recurrence, the same strain was responsible for the initial and recurrent episode in 17 women. For the remaining five women, four had strain replacement and one had a change of species. None of the isolates recovered from the women demonstrated resistance to either clotrimazole or fluconazole. CONCLUSIONS: Our findings support the theory of vaginal relapse and thus may support the use of more prolonged courses of antifungal therapy initially to increase the chances of eradication of the yeast.

Adult↗

[Adolescent contraception. Current trends].

Despite easy availability of contraception, Germany is confronted with the problem of increasing rates of pregnancies and abortions in minors. Prescription of contraceptives that do not rely on compliance and are acceptable to adolescents is required in addition to improved counseling. For that purpose, adherence to the guidelines for the use of contraceptives in minors written by the consortium for legislation in medicine (AG Medizinrecht) is essential. Oral contraceptives are the most commonly prescribed form of birth control, advantages include reversibility as well as a good tolerance and safety profile. New developments are low-dose compounds, novel progestins, prevention of ovulation by pure gestagen pills and the long-term use of low-dose monophasic micro pills. Long-term contraceptives like subdermally implantable depot compounds or hormone-releasing pessaries in utero have been used on a regular basis and seem a convenient alternative for birth control for longer periods, also in adolescents. The easy-to-use intravaginal ring and the birth control patch have expanded the spectrum of hormone-releasing contraceptive systems. Studies show improved compliance and a possible reduction of unintentional pregnancies due to application errors. Amelioration of the range of highly effective birth control products different modes of application will hopefully lead to drop in the rate of unplanned pregnancies, especially in adolescents.

Abortion, Induced↗

Treatment of vaginal candidiasis with miconazole.

An open trial was carried out in 50 women with clinical signs and mycological evidence of vaginal candidiasis to compare the effectiveness of treatment with 2% miconazole cream with that of nystatin pessaries. Both groups were given intravaginal treatment for 14 days and were followed up at monthly intervals for 3 months. Relief of symptoms and clinical signs was comparable in the two groups but the mycological cure rate at 1 month was higher with miconazole. At 2 and 3 months, however, there was no significant difference between the cure rate obtained with the two treatments in the patients still included in the study.

Candidiasis, Vulvovaginal↗

The PAV trial: does lactobacillus prevent post-antibiotic vulvovaginal candidiasis? Protocol of a randomised controlled trial [ISRCTN24141277].

BACKGROUND: Complementary and alternative medicines are used by many consumers, and increasingly are being incorporated into the general practitioner's armamentarium. Despite widespread usage, the evidence base for most complementary therapies is weak or non-existent. Post-antibiotic vulvovaginitis is a common problem in general practice, for which complementary therapies are often used. A recent study in Melbourne, Australia, found that 40% of women with a past history of vulvovaginitis had used probiotic Lactobacillus species to prevent or treat post-antibiotic vulvovaginitis. There is no evidence that this therapy is effective. This study aims to test whether oral or vaginal lactobacillus is effective in the prevention of post-antibiotic vulvovaginitis. METHODS/DESIGN: A randomised placebo-controlled blinded 2 x 2 factorial design is being used. General practitioners or pharmacists approach non-pregnant women, aged 18-50 years, who present with a non-genital infection requiring a short course of oral antibiotics, to participate in the study. Participants are randomised in a four group factorial design either to oral lactobacillus powder or placebo and either vaginal lactobacillus pessaries or placebo. These interventions are taken while on antibiotics and for four days afterwards or until symptoms of vaginitis develop. Women self collect a vaginal swab for culture of Candida species and complete a survey at baseline and again four days after completing their study medications. The sample size (a total of 496--124 in each factorial group) is calculated to identify a reduction of half in post-antibiotic vulvovaginitis from 23%, while allowing for a 25% drop-out. An independent Data Monitoring Committee is supervising the trial. Analysis will be intention-to-treat, with two pre-specified main comparisons: (i) oral lactobacillus versus placebo and (ii) vaginal lactobacillus versus placebo.

Adult↗

Progesterone stimulates luteinizing hormone secretion by acting directly on the pituitary.

To determine if progesterone (P) does affect gonadotropin secretion by acting directly on the pituitary, six women with hypothalamic gonadotropin deficiency were studied. They were treated with 17 beta-estradiol (E2; 2 mg/day, orally) to induce P receptors and maintain constant plasma E2 levels during two 15-day periods separated by 1 month. GnRH was administered iv at a dose of 10 microgram/pulse every 90 min during the last 5 days of E2 treatment. Either P (400 mg/day) or a placebo was administered intravaginally in a cross-over randomized design during the 5 days of pulsatile GnRH therapy. A baseline study of pulsatile LH secretion was performed, with sampling performed every 10 min for 8 h. The sampling was then repeated on day 15 of each study period at the end of pulsatile GnRH administration. Plasma levels of E2 and P were measured every day during the 5 days of either GnRH and P or GnRH and placebo treatment. In the six patients, the observed apulsatile pattern of LH during the baseline study confirmed the diagnosis of complete gonadotropin deficiency. Plasma E2 levels were not significantly different at the time of each pulse analysis (288 +/- 61 vs. 252 +/- 77 pmol/L). The plasma P level achieved with the vaginal pessaries was 22 +/- 5 nmol/L. P treatment resulted in all cases in a significant increase in the mean plasma LH level (5.2 +/- 0.9 vs. 3.6 +/- 0.7 IU/L after GnRH plus placebo; P less than 0.001). Furthermore, LH pulse amplitude was significantly increased by P compared to placebo (3.1 +/- 0.3 vs. 1.4 +/- 0.1 IU/L, respectively; P less than 0.01). Mean plasma FSH levels were significantly increased by GnRH regardless of whether P or placebo was present. In conclusion, these data indicate that a short exposure to physiological levels of P in the range of early luteal phase levels has a stimulatory effect on LH secretion by acting directly at the pituitary level.

Activity Cycles↗

An audit of isolation rates of Candida species from vulval and vaginal sampling.

The clinical features of vulvovaginal candidiasis are the result of the inflammatory response of the vulva and vagina to Candida overgrowth. Topical treatments comprise intra-vaginal pessaries or cream used in combination with a similar azole-based cream for external application. In this audit Candida isolation rates from vulval and vaginal samples were strongly concordant confirming that combined topical treatments should be used for the recommended treatment time to ensure mycological cure.

Candida↗

Recalcitrant Trichomonas vaginalis infection--a case series.

The objective of this study was (1) to estimate the prevalence of recalcitrant Trichomonas vaginalis (TV) infection in a UK genitourinary medicine clinic; (2) to use a case series and literature review to suggest an algorithm for management of recalcitrant TV (rTV). A retrospective review of laboratory records, case-notes and literature review was conducted. Fifteen patients were studied, representing 1.16% of the cases presenting during the study period. A wide variety of therapeutic agents was used, the treatment regimen differed for each patient. No treatment was universally effective in achieving cure, but the use of acetarsol pessaries vaginally appeared to be the most frequently successful strategy. Based on these results, an algorithm for treatment of rTV is presented, although clinical trials will be needed to elucidate the best clinical approaches to this problem.

Algorithms↗

Sexuality and the menopause.

Sexual problems such as dyspareunia and decreased sexual desire are common after the menopause. Hypoactive sexual desire disorder is the diagnostic category applied to many women with loss or lack of sexual interest or desire. The principal components of assessment for sexual dysfunction in menopausal women are: a general, gynaecological, obstetric, psychiatric, psychosexual and relationship history; use of self-report questionnaires; physical examination; and hormonal evaluation. The use of low-dose vaginal estrogen tablets, rings, creams or pessaries may help to improve local genital response but does not necessarily improve sexual interest or motivation. An improvement in sexual function has been reported with tibolone and a combination of estrogen and androgen therapy, al though it remains unclear which groups of postmenopausal women with sexual problems will benefit most from such treatments. Where there is no response to estrogens or where there is premature or surgical menopause the addition of an androgen may be necessary, particularly if the free testosterone levels are low.

Female↗

Vaginal ring delivery of hormone replacement therapy--a review.

Vaginal ring delivery systems are a highly promising approach to hormone replacement therapy (HRT). The vagina is an excellent route for steroid absorption. Menopausal vaginal rings can be designed to allow very low dose local delivery of oestrogen to the vagina for the large percentage of postmenopausal women experiencing urogenital atrophy, or can be modified to deliver much higher doses sufficient for systemic oestrogen replacement therapy, with or without simultaneous progestogen release. Clinical studies of ultra-low dose rings have shown them to be as efficacious as established treatments of urogenital atrophy (creams, pessaries) and to be preferred by most users. Pharmacokinetic and limited clinical studies of vaginal rings designed to deliver systemic doses of HRT (oestrogen alone or combined) have also been highly promising. Vaginal ring delivery of HRT offers women convenient, long-acting therapy (>/= 3 months) that is under their own personal control.

Administration, Intravaginal↗

The return to ovulation following early abortion: a comparison between vacuum aspiration and prostaglandin.

The return to ovulation following early abortion (less than or equal to 56 days amenorrhea) has been assessed after both vacuum aspiration under general anesthesia (N = 14) and menstrual induction with 16,16 dimethyltrans-delta 2PGE1 methyl ester in pessary form (N = 18). The urinary excretion of hCG, total estrogen and pregnanediol was similar in each group. There was an initial rapid decline in hCG excretion (t1/2 48 h), reaching 10% of the pre-treatment value after 6 days. Twenty-nine (91%) women showed a luteal phase rise in pregnanediol excretion, with ovulation occurring on day 29 (16-37) and 24 (16-32) in the vacuum aspiration and prostaglandin groups, respectively (median (range) NS). The wide range in the return of ovarian activity was related to the variation in decline of progesterone secretion (as reflected by excretion of pregnanediol) by the corpus luteum. Asynchrony between the ovarian and menstrual cycles resulting from a delay to ovulation presents a major constraint to the use of early pregnancy interruption as a routine method of fertility control.

Abortion, Induced↗

Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep.

Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin-treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low-affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of small luteal cells without a significant change in luteal mass by Day 3 and, overall, have fewer low-affinity PGF-2 alpha binding sites.

Animals↗

Effect of immunization against the amino-terminal peptide (alpha N) of the alpha 43-subunit of inhibin on follicular atresia and expression of tissue inhibitor of matrix metalloproteinase (TIMP-1) in ovarian follicles of sheep.

Ewes actively immunized against alpha N, the N-terminal peptide of inhibin alpha 43 precursor, have lowered fertility associated with ovulation failure, restricted tissue remodelling and reduced matrix metalloproteinase-2 activity in the follicular fluid at the time of expected ovulation. This could be due to altered ratios of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase (TIMP-1), or to the onset of atresia in antral follicles destined to ovulate. The objectives of the present study were to investigate the effects of immunization against alpha N on the localization of TIMP-1 in ovine follicles, and on follicular growth and atresia in the follicular phase. Ewes were either immunized against alpha N or remained as controls and the ovaries were removed before (0, n = 4) and at 12 h (n = 4) and 24 h (n = 4) after hCG administration in a synchronized follicular phase, 48 h after removal of intravaginal pessaries. Observations were made on a single section taken through the largest follicle present in the ovaries of each ewe. There were no healthy antral follicles > 1 mm in immunized ovaries (0/29) compared with controls (16/31) (P < 0.001), whereas the proportion of healthy antral follicles < 1 mm was the same in each group (9/19 versus 5/12). TIMP-1 immunoactivity was localized in large luteal cells, smooth muscle and endothelial cells, and in all antral follicles, including oocytes. At the time of hCG administration, no TIMP-1 immunoreactivity was detected in the apical region of the follicular wall of large follicles (> 6 mm) compared with the rest of the follicle wall, but staining appeared in the apical granulosa layer 24 h later. In newly formed corpora lutea, TIMP-1 expression was found along the invaginating vascular layer. There was no effect of immunization on the patterns of TIMP-1 immunoreactivity, suggesting that changes in TIMP-1 are not involved in the effects of alpha N. These data are consistent with a paracrine role for alpha N in the selection and atresia of antral follicles, and for TIMP-1 in tissue reorganization and steroidogenesis at the time of ovulation.

Analysis of Variance↗

Effect of immunization against the alpha N (alphaN) and alpha C (alphaC) peptides of the alpha43 subunit of inhibin on antral follicular growth and atresia and the patterns of gonadotrophin secretion in ewes.

The aims of this study were to investigate the role of inhibin in the distribution of healthy and atretic antral follicles and the secretion patterns of gonadotrophins. Ewes were actively immunized against either alphaN or alphaC of the inhibin alpha subunit with a primary injection and three booster injections. The control ewes received adjuvant only. The ovaries were removed either before or at 24 h after hCG administration in a synchronized follicular phase 48 h after removal of intravaginal progesterone pessaries. Morphological observations were made on every fifth section of the complete ovary (one per ewe) stained with haematoxylin and eosin. The mean number of corpora lutea observed per ewe with corpora lutea was not significantly different in ewes immunized against alphaN (2.4; alphaN-immunized ewes) or alphaC (2.6; alphaC-immunized ewes), and control (2.4) ewes, although some corpora lutea appeared cystic in the immunized ovaries. Compared with luteal phase concentrations, mean basal FSH concentrations in the early follicular phase were significantly increased in the alphaC-immunized ewes, similar in alphaN-immunized ewes and reduced in control ewes. No differences were observed in any of the LH parameters. Before hCG treatment, healthy antral follicles > 1 mm in diameter were not observed in any of the 52 follicles in the aC-immunized ewes and were observed in one of 37 follicles from alphaN-immunized ewes compared with 19 of 28 follicles in control ewes (P < 0.0001). For healthy antral follicles < 1 mm in diameter, there were 72 of 85 follicles in the alphaC-immunized ewes, 79 of 81 follicles in the alphaN-immunized ewes and 81 of 82 follicles in the control ewes. Similar results were obtained in healthy antral follicles < 1 mm in diameter at 24 h after hCG administration. In contrast to the control ewes, no healthy preovulatory follicles (> 6 mm in diameter) were observed in alphaN- and alphaC-immunized ewes either before or 24 h after hCG administration. Two newly formed corpora lutea from alphaC-immunized ovaries contained retained oocytes compared with none in control and alphaN-immunized ovaries. In conclusion, immunization against alphaN and alphaC may result in disruption of the normal processes of antral follicular growth and maturation independent of the concentrations of FSH and LH.

Animals↗

Effect of melatonin on the peripheral concentrations of LH and progesterone after oestrus, and on conception rate in ewes.

It has previously been shown that administration of the indoleamine melatonin to advance the breeding season of ewes is also associated with an increase in ovulation rate and subsequent litter size. Experiment 1 assessed whether, in ewes receiving melatonin to advance the breeding season, the indoleamine acts directly on the corpus luteum to enhance progesterone secretion or indirectly through increased activity of the hypothalamic pulse generator. Six ewes received 3 mg melatonin orally at 15.00 h daily from 22 March onwards, six were induced to ovulate during mid-anoestrus following withdrawal of a progestagen pessary and injection of exogenous gonadotrophin and six acted as naturally ovulating controls. First overt oestrus occurred between 17 May and 8 July in melatonin-treated ewes, between 21 October and 3 January in control ewes and on 8 July in all induced ewes. On days 2 and 10 after the first overt oestrus, melatonin-treated ewes had pulsatile LH activity characteristic of that measured in control ewes ovulating naturally during the breeding season. There was an absence of any pulsatile LH activity in the induced ewes. Progesterone concentrations between days 7 and 12 following oestrus were significantly higher in melatonin-treated than in control and induced ewes, suggesting a luteotrophic role for melatonin. Experiment 2 was carried out to determine whether administration of melatonin commencing after induced ovulation and insemination would alter the endocrine status of the ewe and thereby influence the establishment of pregnancy and embryo survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗