Topical reinforcement of the cervical mucus barrier to sperm.

Close to half of the world's pregnancies are still unplanned, reflecting a clear unmet need in contraception. Ideally, a contraceptive would provide the high efficacy of hormonal treatments, without systemic side effects. Here, we studied topical reinforcement of the cervical mucus by chitosan mucoadhesive polymers as a form of female contraceptive. Chitosans larger than 7 kDa effectively cross-linked human ovulatory cervical mucus to prevent sperm penetration in vitro. We then demonstrated in vivo using the ewe as a model that vaginal gels containing chitosan could stop ram sperm at the entrance of the cervical canal and prevent them from reaching the uterus, whereas the same gels without chitosan did not substantially limit sperm migration. Chitosan did not affect sperm motility in vitro or in vivo, suggesting reinforcement of the mucus physical barrier as the primary mechanism of action. The chitosan formulations did not damage or irritate the ewe vaginal epithelium, in contrast to nonoxynol-9 spermicide. The demonstration that cervical mucus can be reinforced topically to create an effective barrier to sperm may therefore form the technological basis for muco-cervical barrier contraceptives with the potential to become an alternative to hormonal contraceptives.

An Open, Uncontrolled Pilot Study on 12-Week Use of VagiVital for Treatment of Vulvovaginal Atrophy in Breast Cancer Patients Undergoing Adjuvant Aromatase-Inhibitor Therapy.

PURPOSE: This pilot study assessed the efficacy of 12 weeks of daily treatment with a vaginal gel based on a water-based cellulose gel in reducing the severity of moderate-severe symptoms of vulvovaginal atrophy (VVA) and followed adverse events in female breast cancer patients undergoing treatment with adjuvant aromatase- inhibitor therapy. METHODS: In this open, uncontrolled pilot study, the efficacy and safety of the gel during a treatment period of 12 weeks (daily 1×1 mL) were evaluated (n=28). The gel is made of water and hypromellose, a hydropropylmetyl cellulose, which works by coating the vagina, and was developed to treat moderate-severe symptoms of VVA. The primary efficacy variable was the most bothersome symptom (MBS; among vulvovaginal irritation and itching, vaginal dryness, dysuria, or dyspareunia) self-identified at baseline on a four-point scale. RESULTS: A total of 28 patients fulfilled all entry criteria and had data available after the start of treatment. Treatment with the gel reduced MBS scores from baseline (n=28, mean 2.71) to week 12 (n=27, mean 1.33, mean reduction 1.37; p=0), and reduced the overall total scores for VVA symptoms from a mean of 5.39 at baseline to 2.25 at week 12 (p=0). Eleven subjects (39%) reported 19 AEs. CONCLUSION: A 12-week treatment with the gel significantly reduced the severity of MBSs and VVA symptoms, improved quality of life, and was safe to use in women with breast cancer undergoing adjuvant aromatase-inhibitor therapy. In view of the beneficial effects of nonhormonal treatments, for cancer patients in particular, the water-based cellulose gel VagiVital is a suitable candidate for first-choice treatment of VVA symptoms in breast cancer patients and in women predisposed to cancer.

A Vaginal Inlay for Reduction of Stress Urinary Incontinence: Outcome of a Randomized Clinical Trial and Four User Acceptance Studies.

A multicenter, randomized, controlled clinical trial and four postmarket user acceptance investigations were carried out to document the safety, performance, and user acceptance of Efemia Bladder Support, a novel vaginal inlay for the temporary reduction of stress urinary incontinence (SUI). The clinical investigation enrolled 97 women diagnosed with SUI, randomized 3 : 1 to either treatment or standard care (control). The primary endpoint was reduction of urine leakage, measured as change in pad weight baseline week compared with treatment week. Secondary endpoints were treatment success, calculated as the percentage of subjects with >70% reduction in pad weight, reduction in incontinence episodes, and quality of life (QoL). 75 women (77%) completed the clinical investigation. No serious adverse events occurred. The treatment group reached a 55% (p < 0.001) mean reduction of total leakage compared to the control arm. A subanalysis, involving only leakage during provocation testing (coughing and jumping), showed a 67% (p < 0.001) mean reduction of leakage. No significant effect on QoL could be observed. 51% of the women answered "yes" to the question if they would use the device to reduce SUI. The user acceptance of the device was further investigated in four postmarket studies, using an improved device design with a slimmer centerpiece and a thinner handle, while keeping the effect achieving parts of the device unchanged. An average of 74% of the 102 participants in the postmarket studies reported that they were likely to continue using Efemia. The highest user satisfaction was seen in the two studies evaluating the use of Efemia during exercise, where 83% and 88% of the women were likely to continue using Efemia. It can be concluded that Efemia is a safe, well-tolerated, and effective alternative for reducing SUI, both in everyday life and during physical exercise.

Correction to: Defined serum- and xeno-free cryopreservation of mesenchymal stem cells.

In the original article, Fig. 1A was by mistakenly duplicated. The corrected image is provided in this correction article.

Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial.

CONTEXT: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models. OBJECTIVE: The objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD. DESIGN: This was an explorative randomized, double-blind, placebo-controlled study. SETTING: Swedish multicentre study with 10 centers. PARTICIPANTS: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott's algorithm. INTERVENTION: Subjects were randomized to treatment with UC1010 (10 or 16mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle. OUTCOME MEASURES: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life). RESULTS: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p=0.041) and borderline significance (p=0.051) for the sum of Negative mood score. Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n=60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p=0.006), and for sum of Negative mood score (p=0.003) and impairment (p=0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study. CONCLUSIONS: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

Annual direct and indirect costs attributable to nocturia in Germany, Sweden, and the UK.

OBJECTIVE: Our aim was to estimate the prevalence-based cost of illness imposed by nocturia (≥2 nocturnal voids per night) in Germany, Sweden, and the UK in an average year. METHODS: Information obtained from a systematic review of published literature and clinicians was used to construct an algorithm depicting the management of nocturia in these three countries. This enabled an estimation of (1) annual levels of healthcare resource use, (2) annual cost of healthcare resource use, and (3) annual societal cost arising from presenteeism and absenteeism attributable to nocturia in each country. RESULTS: In an average year, there are an estimated 12.5, 1.2, and 8.6 million patients ≥20 years of age with nocturia in Germany, Sweden, and the UK, respectively. In an average year in each country, respectively, these patients were estimated to have 13.8, 1.4, and 10.0 million visits to a family practitioner or specialist, ~91,000, 9000, and 63,000 hospital admissions attributable to nocturia and 216,000, 19,000, and 130,000 subjects were estimated to incur a fracture resulting from nocturia. The annual direct cost of healthcare resource use attributable to managing nocturia was estimated to be approximately €2.32 billion in Germany, 5.11 billion kr (€0.54 billion) in Sweden, and £1.35 billion (€1.77 billion) in the UK. The annual indirect societal cost arising from both presenteeism and absenteeism was estimated to be approximately €20.76 billion in Germany and 19.65 billion kr (€2.10 billion) in Sweden. In addition, in the UK, the annual indirect cost due to absenteeism was an estimated £4.32 billion (€5.64 billion). CONCLUSIONS: Nocturia appears to impose a substantial socioeconomic burden in all three countries. Clinical and economic benefits could accrue from an increased awareness of the impact that nocturia imposes on patients, health services, and society as a whole.

Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women.

OBJECTIVE: To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. STUDY DESIGN: Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. RESULTS: The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04). CONCLUSION: Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.

Defined serum- and xeno-free cryopreservation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have vast potential in cell therapy, and are experimentally used in the clinic. Therefore, it is critical to find a serum- and xeno-free cryopreservation method. The aim of this study was to compare two serum- and xeno-free cryoprotectants for MSCs. Adipose tissue MSCs (Ad-MSCs) and bone marrow MSCs (BM-MSCs) were cryopreserved in two cryoprotectants: the defined serum- and xeno-free STEM-CELLBANKER™ (CB) and 10 % dimethyl sulfoxide (DMSO) in a xeno-free serum replacement cell culture medium and compared to non-cryopreserved MSCs. MSCs cryopreserved in CB or DMSO had similar morphology and surface marker expression compared to their respective non-cryopreserved MSC. Ad-MSCs and BM-MSC in both cryoprotectant media exhibited reduced mean fluorescence intensity (MFI) for CD105, BM-MSCs for CD73 and Ad-MSC increased MFI for HLA class I compared to non-cryopreserved MSCs. Population doubling time of CB cryopreserved and non-cryopreserved Ad-MSCs was similar (38.1 ± 13.6 and 36.8 ± 12.1 h), but somewhat higher when cryopreserved in DMSO (42.2 ± 10.8 h). BM-MSCs had higher population doubling time (CB 47.7 ± 11.4 and DMSO 62.3 ± 32.9 h respectively, p < 0.05) compared to Ad-MSCs. The viability of Ad-MSCs was significantly higher after cryopreservation in CB compared to DMSO (90.4 ± 4.5 % vs. 79.9 ± 3.8 % respectively). Ad-MSCs and BM-MSCs retained their mesodermal differentiation potential when cryopreserved in both cryoprotectants. The characteristics of Ad-MSCs post-thawing are better preserved by CB than by DMSO in serum- and xeno-free medium. Furthermore, Ad-MSCs and BM-MSCs are differently affected by the cryoprotectants, which may have implications for cell therapy.

Defined serum-free media for in vitro expansion of adipose-derived mesenchymal stem cells.

BACKGROUND: There is a growing interest in mesenchymal stem cells (MSCs) because they are regarded as good candidates for cell therapy. Adipose tissue represents an easily accessible source to derive mesenchymal stem cells (Ad-MSCs) non-invasively in large numbers. The aim of this study was to evaluate a defined serum-free medium for in vitro expansion of MSCs as a prerequisite for their clinical use. METHODS: Adipose tissue was isolated from healthy donors. Cells were isolated and expanded for five passages in serum-free medium (Mesencult-XF) and Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (DMEM-FBS). MSC morphology, marker expression, viability, population doubling time and differentiation potential toward osteogenic and adipogenic lineages were evaluated. Bone marrow MSCs were included as controls. RESULTS: Ad-MSCs cultured in Mesencult-XF had shorter population doubling time (33.3 ± 13.7 h) compared with those cultured in DMEM-FBS (54.3 ± 41.0 h, P < 0.05). Ad-MSCs cultured in Mesencult-XF displayed a stable morphology and surface marker expression and a higher differentiation potential in comparison to Ad-MSCs cultured in DMEM-FBS. CONCLUSIONS: The defined serum-free and xeno-free Mesencult-XF media appear to be a good choice for Ad-MSCs, but it is not as good in supporting culture of bone marrow MSCs when the cells are to be used for clinical purposes.

Topical oxytocin reverses vaginal atrophy in postmenopausal women: a double-blind randomized pilot study.

INTRODUCTION: Oxytocin is a peptide hormone produced in the hypothalamus and it is best known for its role in labour and lactation. This double-blind, randomized study was performed at Huddinge Hospital of Karolinska Institutet, Stockholm in order to test the effectiveness of topical oxytocin gel in women with postmenopausal vaginal atrophy. METHODS: Twenty postmenopausal women (at least two years after menopause) with symptoms of vaginal atrophy such as vaginal dryness, pain, itching, discomfort and bleeding during intercourse were enrolled in the study when visual inspection of the vagina had confirmed that their mucosa was atrophic. The participants were randomized to intravaginal treatment with either oxytocin or placebo gel for seven days. Before and after treatment, a gynaecological examination and a visual and colposcopic inspection of the vagina were performed, biopsies from the vaginal mucosa were taken and blood samples were collected for analysis of circulating levels of estradiol and oxytocin. RESULTS: Prior to treatment, visual and colposcopic inspection showed that all of the 20 participants had an atrophic vaginal mucosa. After treatment with the oxytocin gel, the examination showed that the vaginal epithelium of seven of the 10 participants in the oxytocin group had become healthier and normalized. No change in these parameters was observed among the 10 participants in the placebo group. This difference between the oxytocin and placebo groups was significant (P= 0.003). Seven participants in the active group and four in the placebo group reported relief of symptoms of vaginal atrophy after seven days of applying the gel. The effect of oxytocin to normalize the morphological appearance of the vaginal mucosa was almost significant when compared with the placebo group (P= 0.07). There was no significant difference between the circulating levels of estradiol and oxytocin in both the oxytocin and placebo groups before and after treatment. None of the participants reported any side-effects. CONCLUSION: Topical treatment with oxytocin appears to improve vaginal atrophy in postmenopausal women. A limitation of this pilot study is that it was based on a small study population hence the results should be regarded with caution. Larger studies are in progress to establish the possibility of using oxytocin as a clinical treatment for vaginal atrophy.

Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder.

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI.

Different estrogen sensitivity of urogenital tissue from women with and without stress urinary incontinence.

AIMS: Oral hormone replacement therapy (HRT) based on estradiol-17beta (E2), E2 esters or conjugated equine estrogens gives rise to huge amounts of circulating estrone (E1) as a result of the first liver pass. E1 is an estrogen (ER) receptor agonist but has also been reported to act as a partial E2 antagonist in vitro. Our aim was to investigate the influence of circulating estrogens on estrogen sensitivity of urogenital tissue collagen turnover in patients with stress urinary incontinence (SUI) and in urologically healthy women, with and without HRT, in view of possible effects of E1 as a partial E2 antagonist. METHODS: Markers of collagen turnover, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and E1 and E2 were analyzed in serum from 54 patients with SUI and 29 urologically healthy women. RESULTS: In the total control group only a significant positive correlation was found between E2 and T-PICP. Lowering the upper serum E1 limit resulted in significant positive correlations also between E2 and T-PIIINP and finally also between E2 and T-ICTP. This pattern was found also in subgroups of post- and premenopausal controls. No association between serum E2 and collagen turnover markers and no effects of lowering the upper serum E1 limit was found in the total and postmenopausal SUI patients, while the correlation pattern in premenopausal SUI patients showed some resemblance to that in the controls. CONCLUSION: At physiological E1 levels E2 increases collagen turnover in urogenital tissue in urologically healthy women but not in women with SUI in general; however, there was a certain effect of E2 in premenopausal but not in postmenopausal SUI patients. Urogenital tissue in SUI patients and in urologically healthy women may differ in estrogen sensitivty and in SUI patients this difference may be related to menopause. Circulating E1, which is present in huge amounts during oral HRT, may act as an estrogen receptor agonist as well as a partial E2 antagonist also in humans in vivo.

Retest reliability of surface electromyography on the pelvic floor muscles.

AIMS: The aim of the current study was to evaluate the retest reliability of repeated intravaginal surface electromyography (surface EMG) of the pelvic floor muscles in healthy women, who were able to perform correct pelvic floor muscle contractions. METHODS: Seventeen nullipara women in the age of 20-35 years completed the measurements. The surface EMG was performed with the subjects in supine position with knees bent. The surface and ground electrodes were attached to a vaginal probe. A total of three test sessions were conducted, two on the same day with 30 minutes apart and a third 26-30 days later. Each test session consisted of three maximum contractions, 10 seconds hold and 10 seconds rest. RESULTS: Average activity, peak, work and baseline showed good to high reliability (ICC = 0.83-0.96). The reliability was somewhat higher in-between test session one and two compared with test session number three. Generally choosing the highest contraction in one test session resulted in a slightly higher ICC than taking an average result of all three contractions. CONCLUSIONS: The current study shows that surface EMG is a reliable method of assessing pelvic floor muscle activity in healthy women. Neurourol. Urodynam. 28:395-399, 2009. (c) 2009 Wiley-Liss, Inc.

Efficacy and safety of duloxetine in elderly women with stress urinary incontinence or stress-predominant mixed urinary incontinence.

OBJECTIVES: To evaluate the efficacy and safety of duloxetine in community-dwelling women > or =65 years with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (S-MUI) versus placebo. METHODS: Patients were randomly assigned for 12 weeks to placebo (N=134) or duloxetine (N=131) (20mg twice daily [BID] for 2 weeks and 40 mg BID for an additional 10 weeks), followed by a double-blind 4-week dose de-escalation/discontinuation phase. The primary efficacy variable was the percent change in incontinence episode frequency (IEF) from baseline to endpoint. Other variables included absolute IEF change, responder rate, changes in mean time between voids (MTBV), weekly continence pad usage, the impact of treatment on quality of life, patient's global impression of improvement (PGI-I), and changes in depression and cognition. RESULTS: Duloxetine-treated patients had a significantly greater decrease from baseline to endpoint in mean IEF/week than placebo-treated patients (-52.47% vs. -36.70%, P<0.001). The IEF responder rate (> or =50% reduction in IEF/week) was 57.1% in the duloxetine group and 35.2% in the placebo group (P<0.001). Significant benefits of duloxetine were also demonstrated for weekly continence pad usage (P=0.011), MTBV (P<0.001), incontinence quality of life questionnaire (I-QOL) scores (P<0.001), and PGI-I ratings (P<0.001). Patients with depressive symptoms and cognitive impairments were few and changes were insignificant. The proportion of patients with > or =1 treatment-emergent adverse event (TEAE) was similar with both treatments, but dry mouth, fatigue, constipation, and hyperhidrosis were significantly more common in women taking duloxetine. CONCLUSIONS: Duloxetine is a safe and effective treatment for elderly women with symptoms of SUI or S-MUI.

Endocrine status and markers of collagen synthesis and degradation in serum and urogenital tissue from women with and without stress urinary incontinence.

AIMS: To investigate possible differences in androgen/estrogen status between patients with stress urinary incontinence (SUI) and healthy women's and to study possible associations between circulating estrogens and androgens on the one hand and collagen synthesis and metabolism in urogenital tissue on the other. METHODS: Markers of collagen turnover, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and the amino-terminal propeptide of procollagen III (PIIINP), were assayed in urogenital tissue homogenates and estradiol-17beta (E2), total testosterone (T), and sex-hormone-binding globulin (SHBG) were assayed in peripheral serum from 58 patients with SUI and 30 urologically healthy women. Apparent concentrations of free testosterone (fT) were calculated from T, SHBG, and a fixed albumin value. RESULTS: Significant positive correlations were found between E2 and PICP in controls and between E2 and ICTP in SUI patients without exogenous hormones. Significant negative and sometimes strong correlations were found between serum T and fT on the one hand and all three collagen turnover markers on the other. These correlations were strengthened when parity and/or body mass index (BMI) were reduced. No correlations between T and fT and collagen turnover markers were found in the controls. There were no significant differences between any of the groups in serum E2, T, or fT. CONCLUSION: Estrogens may increase collagen turnover in urogenital tissue, however, the clinical significance of this is still unclear. Androgens may affect urogenital tissue negatively by slowing down collagen turnover, probably by inhibition of matrix metalloprotease (MMP) synthesis and/or activity. Urogenital tissue in SUI patients and in urologically healthy women may differ in androgen sensitivity.

Conjugated estrogen/progestagen versus tibolone hormone replacement therapy in postmenopausal women: Effects on carbohydrate metabolism and serum sex hormone-binding globulin.

OBJECTIVE: To study the effects of different types of continuous hormone replacement therapy on carbohydrate metabolism. METHOD: Postmenopausal women were treated with conjugated estrogens, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg (CEE/MPA) or tibolone 2.5 mg daily for 13 28-day cycles. Serum glucose and insulin were measured before and during a 75 g oral glucose tolerance test (OGTT) at baseline and after 3, 6 and 13 cycles and areas under the curve (AUC) were calculated. Sex hormone-binding globulin (SHBG) was measured as an additional marker of nutritional and insulin status. RESULTS: Neither CEE/MPA 2.5mg nor tibolone had any effects on carbohydrate metabolism while AUC(insulin), AUC(glucose) and also body mass index (BMI) increased after 13 cycles of treatment in the CEE/MPA 5 mg group. SHBG increased significantly during CEE/MPA treatment and decreased significantly during treatment with tibolone. The effects on SHBG were less pronounced in the CEE/MPA 5mg group. Pretreatment SHBG showed significant negative correlations to BMI and to variables that may reflect a certain degree of insulin resistance, the most pronounced being fasting glucose. Changes in SHBG during treatment with tibolone were negatively correlated to pretreatment SHBG and positively to BMI, AUC(insulin) and fasting insulin resistance index, while no such correlations were found in the CEE/MPA groups. There were no correlations between changes in AUC(insulin) and AUC(glucose) on one hand and basal variables or treatment SHBG on the other in the CEE/MPA groups. CONCLUSION: The effects of tibolone and CEE/MPA on carbohydrate metabolism were considered to have clinical significance only for CEE/MPA 5mg, indicating a less favourable role of the higher progestagen dose. The results further support the important role of metabolic and insulin status in the physiological regulation of SHBG and also indicate that the suppressive effect of tibolone on circulating SHBG is mainly depends on pretreatment SHBG levels. SHBG does not reflect changes in carbohydrate metabolism during CEE/MPA treatment.

Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence.

AIMS: Multiparity and obesity are risk factors for stress urinary incontinence (SUI), but collagen synthesis and metabolism in the urogenital tissue itself may also affect its function and control of micturition. Whether changes in synthesis or degradation of collagen are part of the etiology of SUI is not known and published studies show diverging results. The aims of the present study was to investigate collagen turnover in urogenital tissue in women with SUI (n=71) and in urologically healthy women (n=31). METHODS: Markers of collagen synthesis and breakdown, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and peripheral serum. RESULTS: In the total clinical material SUI patients were significantly older, had a significantly higher body mass index (BMI) and significantly lower serum PICP and tissue ICTP levels than the controls. When healthy controls were compared with SUI patients matched for age, BMI, parity, and hormonal/menopausal status (31 women in each group), the SUI patients had significantly lower serum concentrations of PICP and significantly lower tissue concentrations of PIIINP and ICTP than the controls. Within the total material of SUI patients, post-menopausal women with weak and strong HRT and pre-menopausal women had significantly lower S-ICTP concentrations than untreated post-menopausal patients. Significant negative correlations to parity were found for T-PIIINP and T-PICP and to BMI for T-ICTP. CONCLUSIONS: The low tissue collagen marker levels in women with SUI suggest a reduced collagen turnover, which may negatively affect tissue strength and elasticity.