Search

Background: Erythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS). Methods: 24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo. Results: During IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2–13.4 IU/L and 12.5; 10.3–13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4–19.2 IU/L vs. 10.2; 8.8–12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1. Conclusions: Circulating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo's involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: To assess quality of life (QoL) and sexual function outcomes at 3 years after tension-free vaginal tape (TVT) and polyacrylamide hydrogel injection (PAHG) for stress urinary incontinence (SUI). Methods: In this randomized trial comparing TVT (n = 104) and PAHG (n = 108), we assessed changes in QoL and sexuality using the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire, Short Form (IIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and RAND-36 Item Health Survey (RAND-36) at baseline and at 3 years. This is a secondary analysis of a randomized, noninferiority trial comparing patient satisfaction after TVT and PAHG. Results: In both groups, incontinence-related QoL improved from the baseline (p < 0.00), except for difficulty emptying the bladder and pain/discomfort. Total scores of UDI-6 and IIIQ-7 were lower for TVT compared to PAHG (p < 0.00) indicating better QoL at 3 years. Urinary incontinence with sexual activity or fear of incontinence restricting sexual activity improved in both groups (p < 0.00), with higher scores for physical section subscale in PISQ-12 (p = 0.02) for TVT. Physical and social functioning (RAND-36) improved from the baseline in both groups (p < 0.01) with a better outcome in the TVT group for physical functioning (p = 0.00). Conclusions: Both TVT and PAHG improve QoL and sexual function in primary SUI with better incontinence and health-related QoL scores in the TVT group compared to the PAHG group at 3 years. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7–12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17β-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography–tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan–Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (

The marked sexual dimorphism prevalent in inflammatory/autoimmune diseases is mostly due to sex hormone actions. One common eye disease that disproportionately affects women is dry eye. Thus, our aim was to optimise our highly sensitive liquid chromatography–tandem mass spectrometry method for steroid hormone quantification in tear fluid (TF). We used tears and matched serum samples from 10 heathy individuals. Estrone, estradiol testosterone, progesterone, androstenedione, and dehydroepiandrosterone, were quantified with an HPLC coupled with a Triple Quad 5500 MS. Estrone was measured in 80% of female and 20% of male TF samples (mean ± SD, 68.9 ± 62.2 pmol/L), whereas estradiol was undetectable in tears. Progesterone was identified in half of the female tear samples (2.91 ± 3.47 nmol/L) but in none of the male samples, whereas testosterone was quantifiable only in male tears (0.24 ± 0.1 nmol/L). TF hormone levels were, on average, from 1.4% to 55% of systemic values. Estrone, progesterone, and testosterone levels in tears correlated with the matching serum samples (r = 0.82, 0.79, and 0.85, respectively), but androstenedione and dehydroepiandrosterone showed no correlations. Our LC–MS/MS method could detect five out of the six steroid hormones studied in individual human TF samples and could therefore be used to analyse the role of sex steroids in eye diseases. [ABSTRACT FROM AUTHOR]

Background: Childbirth experience has been shown to depend on the mode of delivery. However, it is unclear how labour induction influences the childbirth experience in different modes of delivery. Thus, we assessed the childbirth experience among mothers with spontaneous and induced labours.Design: A retrospective cohort study.Setting: Childbirths in four delivery hospitals in Helsinki and Uusimaa District, Finland, in 2012-2018.Sample: 95051 childbirths excluding elective caesarean sections.Methods: Obstetric data combined to maternal childbirth experience measured by Visual Analogue Scale (VAS) was analysed with univariate linear modelling and group comparisons. The primiparas and multiparas were analysed separately throughout the study due to the different levels of VAS.Main Outcome Measures: Maternal childbirth experience measured by VAS.Results: The negative effect of labour induction on the childbirth experience was discovered in each mode of delivery. Operative deliveries were perceived more negatively when they were preceded by labour induction. The rate of poor childbirth experience (VAS≤5) was higher for mothers with labour induction (ORs varying from 1.43 to 1.77) except in emergency caesarean sections. The negative effect of labour induction was smaller than the effect of mode of delivery, while successful vaginal delivery with induction (meanPRIMI=8.00 [95% CI 7.96-8.04], meanMULTI=8.50 [8.47-8.53]) was perceived more positive than operational deliveries with spontaneous labour (meansPRIMI≤7.66 [7.61-7.70], meansMULTI≤7.96 [7.89-8.03]). However, labour induction more than doubled the risk of caesarean section for both primiparas and multiparas.Conclusions: Labour induction generates more negative experiences for both primiparas and multiparas. The negative effect of labour induction is detected for all modes of delivery, being worst among labour induction resulting in operative delivery. The parturients facing cumulative obstetric interventions require special support and counselling during and after delivery. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: To assess changes in quality of life (QoL) and sexual function outcomes at 1 year after tension-free vaginal tape (TVT) versus polyacrylamide hydrogel injection (PAHG). Methods: In a randomized trial comparing TVT (n = 111) and PAHG (n = 113) treatments of stress urinary incontinence (SUI), we compared urinary incontinence and health-related QoL using the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire, Short Form (IIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and RAND-36 Item Health Survey (RAND-36) at baseline and 1 year. Results: UDI-6 and IIQ-7 showed improved incontinence-related QoL (p = 0.001) from baseline in both groups except for difficulty emptying the bladder and pain/discomfort. At 1 year, TVT patients experienced less urinary symptom-related distress compared to PAHG (p < 0.001). Sexual function improved in both groups (p < 0.001 for TVT and p = 0.01 for PAHG) with higher scores for the physical section subscale (p < 0.001) for TVT. Health-related QoL (RAND-36) improved from baseline in both groups in physical and social functioning (p < 0.001) with better outcome in the TVT group for physical functioning (p < 0.001). Increase in pain from baseline (p = 0.02) was detected for TVT, but not for PAHG. However, there was no difference between the groups (p = 0.78). Conclusions: In primary SUI, TVT and PAHG treatments both improved QoL and sexual function at 1 year. However, incontinence and health-related QoL scores were better in the TVT group. More pain compared to the baseline was reported after TVT, although there was no difference between groups. Clinical significance needs to be evaluated in long-term follow-up. [ABSTRACT FROM AUTHOR]

Introduction and hypotheses: There is no consensus regarding pregnancy after mid-urethral sling (MUS) operation, and some clinicians recommend postponing the MUS operation if a woman considers further pregnancies or routinely suggest cesarean section as the delivery method after MUS operations. Our primary aim was to assess the risk for stress urinary incontinence (SUI) re-procedure after delivery in women with a MUS operation prior to pregnancy. We also analyzed SUI re-visits and MUS-related complications during pregnancy and postpartum. Methods: We conducted a register-based case-control study of women with a MUS operation in Finland during 1996–2016. We identified 94 cases with a subsequent pregnancy and 330 controls without subsequent pregnancies matched by age, operation type and year. Results: The median follow-up time was 10.7 years (IQR 7.1–13.7). The number of SUI re-procedures did not differ between the cases (n = 3, 3.2%) and controls (n = 17, 5.2%; OR 0.6, 95% CI 0.2–2.1). There was no significant difference in re-visits for stress or mixed urinary incontinence between the cases (n = 23, 24.5%) and controls (n = 86, 26.1%; OR 0.9, 95% CI 0.5–1.6), but 35% of the re-visits in the case group occurred already before the delivery after MUS. The rate of vaginal delivery was lower after MUS operation (57%) than in deliveries before MUS (91%, P < 0.001). Conclusions: Pregnancy after MUS did not increase the odds for SUI re-procedure or re-visit. Considering on our results, future pregnancy does not need to be viewed as an absolute contraindication for MUS operation. [ABSTRACT FROM AUTHOR]

Background: Hysterectomy rates are decreasing in many countries, and virtual reality simulators bring new opportunities into residents' surgical education. The objective of this study was to evaluate the effect of training in laparoscopic hysterectomy module with virtual reality simulator on surgical outcomes among residents performing their first laparoscopic hysterectomy.Methods: This randomized study was carried out at the Department of Obstetrics and Gynecology in Helsinki University Hospital and Hyvinkää Hospital. We recruited twenty residents and randomly signed half of them to train ten times with the laparoscopic hysterectomy module on a virtual reality simulator, while the rest represented the control group. Their first laparoscopic hysterectomy was video recorded and assessed later by using the Objective Structured Assessment of Technical Skills (OSATS) forms and Visual Analog Scale (VAS). The scores and surgical outcomes were compared between the groups.Results: The mean OSATS score for the Global Rating Scale (GRS) was 17.0 (SD 3.1) in the intervention group and 11.2 (SD 2.4) in the control group (p = 0.002). The mean procedure-specific OSATS score was 20.0 (SD 3.3) and 16.0 (SD 2.8) (p = 0.012), and the mean VAS score was 55.0 (SD 14.8) and 29.9 (SD 14.9) (p = 0.001). Operative time was 144 min in the intervention group and 165 min in the control group, but the difference did not reach statistical significance (p = 0.205). There were no differences between the groups in blood loss or direct complications.Conclusion: Residents training with a virtual reality simulator prior to the first laparoscopic hysterectomy seem to perform better in the actual live operation. Thus, a virtual reality simulator hysterectomy module could be considered as a part of laparoscopic training curriculum. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Long-term safety concerns have risen over the mid-urethral sling operation (MUS) for stress urinary incontinence (SUI), which in some countries has led to litigations and even suspending MUS insertions. We examined the long-term re-procedure rate after MUS operations. The main outcome was re-procedures for SUI. The secondary outcome was surgical interventions due to complications. Methods: We analysed a retrospective population cohort of 3531 women with MUS operations in 2000–2006 and followed them up until 31 December 2016. Data were collected from a national hospital register and from hospital patient records. Results: The median follow-up time was 13 years (IQR 11.6–14.8) for the 3280 women with a retropubic MUS (RP-MUS) and 11 years (IQR 10.3–11.9) for the 245 women with a transobturator MUS (TO-MUS). The cumulative number of re-procedures for SUI was 16 (0.5%) at 1 year, 66 (1.9%) at 5 years, 97 (2.8%) at 10 years and 112 (3.2%) at 17 years. This risk was higher after TO-MUS than after RP-MUS operations (OR 3.6, 95% CI 2.5–5.2, p < 0.001). The cumulative number of any long-term re-procedure was 43 (1.2%) at year 1, 105 (3.0%) at year 5, 144 (4.1%) at year 10 and 163 (4.6%) at year 17. Conclusions: Re-procedures occur up to 17 years after primary MUS insertion, but their incidence is low after the first few postoperative years. Re-procedures for recurrent SUI are more common after TO-MUS than RP-MUS. [ABSTRACT FROM AUTHOR]

Background: Gynecological surgery and resident education have changed during recent decades, thus impacting surgical training. Training on simulators must begin before operating on patients. The objective of this study was to evaluate the effect of a simple curriculum on the surgical outcome of the participants' first operative laparoscopy.Methods: This randomized prospective interventional study was carried out in Helsinki University Hospital and Hyvinkää Hospital. We recruited twenty junior residents in Obstetrics and Gynecology, of which half formed a control group and the rest completed the intervention with a theoretical and a practical part. The participants' first laparoscopic salpingectomy was assessed from video recordings by using Objective Structured Assessment of Technical Skills (OSATS) forms and the Numeric Rating Scale (NRS). The surgical outcome and assessed scores were compared between the groups.Results: We found no differences in operative time, blood loss, or complications, nor in OSATS or NRS scores. In the intervention group, participants with the weakest performances in the simulator, seemed to benefit from the training program more than the participants with the best performances (skill level elevation 29.2-31.6% vs. 21.1-23.3%, respectively). The participants with the best performances in the simulator were scored among the best in the recorded operations as well.Conclusion: In this study, we found no difference in the surgical outcome between the groups. However, the participants with low starting levels in the simulator could elevate their skill levels more, though they did not reach the skill level of those with a high starting level. Consequently, we found elevation in skills levels in the simulator tasks, but not in the surgical outcome. Likely, our simple training program with a fixed number of repetitions was insufficient to reach a plateau in the learning curve, and thus the training program in such a curriculum should be proficiency based. [ABSTRACT FROM AUTHOR]

Purpose: Midurethral slings are a well-established treatment option in women suffering stress urinary incontinence. Various different products and methods are used, therefore, the aim of our study was to compare two inside-out retropubic slings (TVT exact® vs. RetroArc®) inserted in two different ways regarding perioperative and mid-term outcomes.Methods: In this prospective randomized controlled non-inferiority multicentre trial, primary endpoint was postoperative cure rate, both objective (negative cough test) and subjective (absence of leakage during physical activity using the UDI-6 questionnaire). Secondary endpoints were patients' satisfaction (Likert scale; ICIQ-UI-SF questionnaires). In addition, intra-and postoperative complications were evaluated. The TVT®-group was operated with an empty bladder, a 18 CH catheter was used with a straight inserter as instructed. Patients randomized into the RetroArc®-group were operated without inserter leading to a reduced catheter size (14 CH), bladder was filled (200 ml) during the procedure.Results: Of the 303 women, 152 were randomized to the TVT® and 151 to the RetroArc® operation. At 3 months, n = 288 (95.0%) and at 12 months n = 229 (75.6%) were assessed. In postoperative objective cure the RetroArc®-procedure was not inferior to TVT® (p = 0.144). In subjective cure, however, the TVT exact® procedure achieved significant better results (TVT® 76.1%, RetroArc® 54.3%, p = 0.002). Perioperative complications were in majority voiding difficulties and lower after the TVT exact®-procedure.Conclusions: Retropubic sling procedures are safe and successful to treat female stress urinary incontinence. However, different materials and techniques result in differences between outcomes also experienced surgeons should be aware of. [ABSTRACT FROM AUTHOR]

Purpose: Mirabegron, a β3-adrenoreceptor agonist, is used to treat overactive bladder. The factors affecting persistence of mirabegron use or symptom improvement are not thoroughly known, but could be related to patient characteristics. Therefore, we evaluated persistence of medication use, symptom improvement, and quality of life among Finnish mirabegron users. In addition, we assessed possible predictors of change in these variables. Materials and Methods: Participants (52 men, 118 women) with an initial mirabegron prescription were recruited nationwide from 79 pharmacies. Volunteers were interviewed at baseline and after 6 months. Subject and clinical characteristics, symptom severity, and quality of life (EQ-5D-5L) were assessed using a visual analogue scale. Results: Of 170 participants, 144 (84.7%) were reached after 6 months. The rate of persistent mirabegron use was 50.7%. Experiencing adverse effects (29.6%) was the most common reason for discontinuation of medication. A primary health care unit as a prescription site (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.03-4.9) was associated with increased risk for discontinuation. Mirabegron relieved symptoms in 45.2% and enhanced quality of life in 41.7% of the participants. Age <64 years was associated with better probability of symptom improvement (OR, 2.7; 95% CI, 1.1-6.8), whereas none of the other parameters assessed predicted change in quality of life. Conclusions: In this Finnish population, 50.7% of the participants continued using mirabegron after 6 months. The prescription site seemed to be important for persistent use, which may be related to patient counseling. Younger patients were more likely to benefit from treatment with mirabegron. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we compared the use of such HT regimens and tibolone in women with and without SUI.Methods: The women with a history of SUI operation (N = 15,002) were identified from the Finnish National Hospital Discharge Register, and the control women without such an operation (N = 44,389) from the Finnish Central Population Register. The use of HT was traced from the National Drug Reimbursement Register, and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were calculated by using the conditional logistic regression analysis.Results: The cases had used any HT more often than the controls. The use of systemic estradiol-only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR 3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of estradiol with noretisterone acetate showed a higher risk of increase than that with medroxyprogesterone acetate. Age over 55 years at the initiation of systemic HT was accompanied by a higher SUI risk increase than that under 55 years of age. The use of tibolone, an estradiol + levonorgestrel-releasing intrauterine device, or vaginal estradiol also increased the risk.Conclusions: The use of HT regimens may predispose to the de novo development or worsening of pre-existing SUI. Thus, caution is needed when these regimens are prescribed to women with mild stress-related urine leakage or with established SUI risk factors. [ABSTRACT FROM AUTHOR]

Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Study Question: Does the use of post-menopausal vaginal estradiol (VE) affect the mortality risk for coronary heart disease (CHD) and stroke.Summary Answer: The use of VE reduces the risk for cardiovascular mortality.What Is Known Already: A growing number of women use VE for post-menopausal genitourinary symptoms. Although this therapy is intended to have only local effects, estrogen is absorbed into the blood circulation and thus VE use may also have systemic effects.Study Design, Size, Duration: We studied a nationwide cohort in Finland 1994-2009 during which post-menopausal women (n = 195 756) initiated the use of VE (age [mean ± SD] 65.7 ± 10.9 years). Follow-up data gathered 1.4 million women-years and we assessed the mortality risk due to CHD (n= 9656) or stroke (n = 4294).Participants/materials, Setting, Methods: The mortality risk in VE users was compared with that in the age-matched background population (standardized mortality ratio; [SMR]; 95% confidence interval) and related to various durations of exposure to VE (1 to ≤3, >3 to ≤5, >5 to ≤10 and >10 years).Main Results and the Role Of Chance: The use of VE was accompanied by decreases in the risk for CHD and stroke death. The risk reduction for CHD death was highest for >3 to ≤5 years exposure (SMR 0.64; 0.57-0.70) and for stroke for >5 to ≤10 years exposure (SMR 0.64; 0.57-0.72). The risk reductions for both CHD and stroke mortality were detected in all age groups with the highest risk reduction being in women aged 50-59 years (SMR 0.43; 0.19-0.88 and SMR 0.21; 0.06-0.58, respectively).Limitations, Reasons For Caution: Our series lack a placebo arm and thus, may harbor a healthy woman bias. Moreover, data on clinical variables such as weight, smoking, blood pressure and family background were unobtainable for this study. Women using both VE and systemic hormone therapy (HT) were included in the comparator background population. This should not cause any significant error because the proportion of women using VE or other HT was modest (<10% in age-matched population) and because the use of systemic HT also reduces death risks in the same population. Our data cannot be directly applied for local regimens containing conjugated equine estrogens, because they are absorbed differently and may show effects that differ from those of estradiol.Wider Implications Of the Findings: In 1000 women using VE for up to 10 years, a maximum of 24 fewer CHD deaths and 18 fewer stroke deaths is likely to occur.Study Funding/competing Interests: This work was supported by unrestricted grants from the Päivikki and Sakari Sohlberg Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, Finska Läkaresällskapet, the Orion Farmos Research Foundation, the Paavo Nurmi Foundation and a special governmental grant for health sciences research. The funding sources had no role in the study design, data handling or manuscript preparation. EPID Research is a company that performs financially supported studies for several pharmaceutical companies. Dr Korhonen, Dr Hoti and MSc Vattulainen, employed by Epid Research, report financial activities from several other pharmaceutical companies outside the submitted work. Dr Mikkola has been a speaker and/or received consulting fees from Mylan and Novo Nordisk. Dr Tuomikoski has been a speaker and/or received consulting fees from Orion and Mylan. The remaining authors report no conflict of interest. [ABSTRACT FROM AUTHOR]

Objective: Adipose tissue is an important extragonadal site for steroid hormone biosynthesis. After menopause, estrogens are synthesized exclusively in peripheral tissues from circulating steroid precursors, of which the most abundant is dehydroepiandrosterone sulfate (DHEAS). Our aim was to study activity of steroid sulfatase, an enzyme hydrolyzing DHEAS, and expression of steroid-converting enzyme genes in subcutaneous and visceral adipose tissue derived from pre- and postmenopausal women. Design: Serum and paired abdominal subcutaneous and visceral adipose tissue samples were obtained from 18 premenopausal and seven postmenopausal women undergoing elective surgery for non-malignant reasons in Helsinki University Central Hospital. Methods: To assess steroid sulfatase activity, radiolabeled DHEAS was incubated in the presence of adipose tissue homogenate and the liberated dehydroepiandrosterone (DHEA) was measured. Gene mRNA expressions were analyzed by quantitative RT-PCR. Serum DHEAS, DHEA, and estrogen concentrations were determined by liquid chromatography-tandem mass spectrometry. Results: Steroid sulfatase activity was higher in postmenopausal compared to premenopausal women in subcutaneous (median 379 vs 257 pmol/kg tissue per hour; P=0.006) and visceral (545 vs 360 pmol/kg per hour; P=0.004) adipose tissue. Visceral fat showed higher sulfatase activity than subcutaneous fat in premenopausal (P=0.035) and all (P=0.010) women. The mRNA expression levels of two estradiol-producing enzymes, aromatase and 17α-hydroxysteroid dehydrogenase type 12, were higher in postmenopausal than in premenopausal subcutaneous adipose tissue. Conclusions: Steroid sulfatase activity in adipose tissue was higher in postmenopausal than in premenopausal women suggesting that DHEAS, derived from the circulation, could be more efficiently utilized in postmenopausal adipose tissue for the formation of biologically active sex hormones. [ABSTRACT FROM AUTHOR]

Objective To assess trends for hysterectomy methods in the Nordic countries and to compare outcomes of hysterectomies in Finland done by trainees with those done by specialists. Design Register-based study. Setting NOMESCO database for the Nordic countries and the Finnish Hospital Discharge Register. Population National prospective cohort of 5279 hysterectomies in Finland. Methods Numbers of hysterectomies in the Nordic countries were collected in 1995-2011 and in Finland in 1990-2012. The Finhyst study to collect data on hysterectomies for benign indications was carried out in Finland in 2006. Information concerning patients, surgeons, and hysterectomy outcome was analysed. Main outcome measures Hysterectomy numbers and methods. Operating time, blood loss, and complications in hysterectomies done by trainees and specialists. Results In Finland, the rate of hysterectomies has been reduced by approximately 50% since the 1990s and is now similar to that in the other Nordic countries. The laparoscopic method is twice as common in Finland as in other Nordic countries, constituting 35-40% of all hysterectomies. The operating time for all hysterectomy methods was 16-25% longer among trainees than specialists. For the abdominal or laparoscopic methods there were no significant differences in the complication rates between the groups. In the vaginal approach, blood loss of ≥1000 mL was slightly more common in operations done by trainees (1.3% vs. 2.6%, p = 0.037). Conclusions Laparoscopic hysterectomy is more common in Finland than in the other Nordic countries. Although trainees need more time to operate, there were no differences between the trainees and the specialists with regard to major complication rates. [ABSTRACT FROM AUTHOR]

Objective To study the possible association between menopausal hot flushes and bone mineral density. Design Observational study. Setting University clinic. Population Healthy women ( n = 143) with or without hot flushes, 6-36 months postmenopausal after participating in a 6-month hormone therapy trial. Methods The women prospectively recorded the number and severity of hot flushes for 2 weeks. Bone mineral density in lumbar and hip bones was measured with dual-energy X-ray absorptiometry at recruitment and reassessed in 114 women approximately 6.2 years later. Main outcome measures Hot flushes and bone mineral density. Results At recruitment, hot flushes were absent in 22 women, mild in 32, moderate in 28, and severe in 61. Lumbar bone mineral densities in non-flushing women (1.130 ± 0.022 g/cm2; mean ± SEM), and in those with mild (1.088 ± 0.024 g/cm2), moderate (1.082 ± 0.030 g/cm2) or severe (1.102 ± 0.019 g/cm2) hot flushes did not differ, nor were there differences in hip bone mineral densities between the four study groups. During the follow-up, lumbar bone mineral density decreased by a mean of 0.4 ± 0.1% a year in women not using hormone therapy, and increased by 0.1 ± 0.2% a year in hormone therapy users ( p = 0.019). The respective non-significant changes in left and right total hip bone mineral densities were - −0.6 ± 0.01 and −1.0 ± 0.1 for the non-users, and −0.4 ± 0.1 and −0.6 ± 0.2 for hormone therapy users. These changes in bone mineral density bore no relation to the hot flush status at baseline. Conclusion In recently menopausal women, hot flushes do not appear to determine bone mass density. [ABSTRACT FROM AUTHOR]

In women, cardiovascular disease (CVD) accounts for about half of all deaths in Western countries. It is generally accepted that endogenous estrogen protects premenopausal women from CVD. However, whether postmenopausal hormone therapy (HT) confers cardiovascular benefit or harm remains controversial. One of the most pronounced factors modifying the cardiovascular effects of HT is age or time since menopause at the initiation of HT. Recently also the impact of hot flushes on CVD risk and the outcomes of HT has gained attention. This review summarizes the newest data regarding HT and CVD in recently postmenopausal women aged 50-59 years in light of the results from older HT trials. The aim is to help clinicians counsel their patients regarding the individual risks and benefits associated with HT use in this age group, where HT use is most prevalent. [ABSTRACT FROM AUTHOR]

Objective To compare in controlled cardiovascular autonomic function tests the effects of hormone therapy ( HT) on heart rate variability ( HRV) responses in postmenopausal women with and without pretreatment hot flushes. Design A randomized placebo-controlled trial. Setting Finland, Helsinki University Central Hospital. Population A total of 150 recently postmenopausal and healthy women with prospectively evaluated hot flushes. Methods Women (72 with and 78 without hot flushes) were randomized to receive estradiol alone or in combination with medroxyprogesterone acetate or placebo for 6 months. Time and frequency domain measures of HRV were assessed at baseline and after HT with short-term recordings during paced quiet and deep breathing and with active orthostatic tests, both under carefully controlled laboratory conditions to avoid confounding factors present in long-term ambulatory HRV measurements. Main outcome measures Responses of time and frequency domain measures of HRV to HT. Results At baseline HRV was similar in women with and without hot flushes. Pretreatment hot flushes did not associate with changes in time domain parameters of HRV during controlled quiet or deep breathing or active orthostatic tests after different types of HT. However, HT reduced HRV in very low frequency power in women with pretreatment hot flushes (from 371 ± 40 to 258 ± 28 ms2, p = 0.018). HT did not have an effect on other frequency domain measures during quiet breathing or active orthostatic tests. Conclusions Hormone therapy did not significantly modify the HRV responses in women with or without hot flushes under controlled short-term measurements of the cardiovascular autonomic nervous system. [ABSTRACT FROM AUTHOR]

Objective Both smoking and the release of nitric oxide ( NO) in the uterine cervix are determinants for high-risk human papillomavirus (hr HPV) infection. We compared the cervical NO release between smoking and non-smoking women with and without hr HPV infection. Design Open clinical cohort study. Setting University Hospital in Finland. Population One hundred and twenty-five smoking and 301 non-smoking women, with ( n = 244) and without ( n = 182) hr HPV infection. In total, 264 women showed cytological and/or histological cervical epithelial changes. Methods The presence of hr HPV was tested by an HPV DNA test and the release of NO was assessed from NO metabolites in the cervical fluid by the Griess reaction. Main outcome measures The difference in cervical NO release between smoking and non-smoking women with and without hr HPV. Results Infection with hr HPV in smokers (70%) was more frequent ( p = 0.001) than in non-smokers (52%). As a whole, smoking was accompanied by a 35% decrease ( p = 0.04) in NO release in hr HPV-infected women (35.9 μmol/L, 95% confidence interval 27.0-44.2) compared with non-smoking hr HPV- infected women (48.3 μmol/L, 95% confidence interval 38.0-56.2). No difference in NO release between smokers and non-smokers was seen in women with healthy cervical epithelium, but smoking was accompanied by a suppressed (26%) NO release ( p = 0.03) in women with either cytological or histological changes. Conclusions Smoking may suppress NO release in the uterine cervix in women with hr HPV infection. [ABSTRACT FROM AUTHOR]

Introduction: Sex-related physiological differences result in different expressions of diseases for men and women. Data are contradicting regarding the increase in the female risk for cardiovascular disease (CVD) at mid-life. Thus, we studied possible sex differences in age-adjusted mortality for CVD and non-vascular diseases stratifying our findings by specific age groups. Methods: Over one million deaths (1 080 910) reported to the Finnish nationwide Causes of Death Register in 1986–2009 were analyzed. A total of 247 942 male deaths and 278 752 female deaths were of CVD origin, the remaining deaths were non-vascular. The annual mortality rates were calculated per 100 000 mid-year population, separately for men and women in 5-year age categories. Results: The age-standardized risk of death from CVD was 80% higher for men (442/100 000) than for women (246/100 000). After age 45–54 the male CVD mortality rate elevated parallel to the non-vascular mortality, whereas in women the CVD mortality elevated considerably more rapidly than the non-vascular mortality from age 60 years onwards. Conclusions: Heart disease mortality in men accelerates at a relatively young age, but in women the risk shows a steep increase at approximately 60 years of age. These data emphasize the need to identify and prevent risk factors for CVD, especially in women in their mid-life years. [ABSTRACT FROM AUTHOR]

Introduction. Levels of nitric oxide metabolites are elevated in the cervical fluid of women with high-risk human papillomavirus (hrHPV). To elucidate the origin of this elevation we studied the cervical expression and localization of endothelial and inducible nitric oxide synthases (eNOS, iNOS) in women. Material and methods. Expression of eNOS and iNOS was studied by Western blotting in the uterine cervixes of 86 women with ( n = 41) and without ( n = 45) hrHPV infection. The localization of eNOS and iNOS in cervical cells was studied by immunohistochemistry in 32 randomly selected women. Results. Expression of eNOS and iNOS (in mean [95% CI] density units relative to actin) was higher in women with hrHPV versus those without (eNOS: 33.8 [22.5-45.1] versus 20.2 [6.1-34.3], P = 0.007; iNOS: 12.0 [7.1-16.9]) versus 5.6 [2.0-9.2], P = 0.003). Smoking reduced 64% eNOS ( P = 0.001) and 68% iNOS ( P = 0.008) in women with hrHPV. Endothelial NOS was localized in the vascular endothelium, while iNOS was present in basal squamous epithelial cells. Low-grade histological lesions were accompanied by elevated expression of both eNOS and iNOS. Conclusions. High-risk HPV-associated elevation in cervical fluid nitric oxide metabolites results from both eNOS and iNOS stimulation. However, smoking seems to suppress this stimulation in hrHPV-infected women. [ABSTRACT FROM AUTHOR]

Objective. To compare cervical fluid nitric oxide release in women with and without Chlamydia trachomatis and high-risk human papillomavirus infection (hrHPV). Design. An open clinical study. Setting. University Hospital of Helsinki. Population. Thirty-nine women with ( n=21) and without C. trachomatis ( n=18). Methods. Chlamydia trachomatis and/or hrHPV were studied by using specific RNA- and DNA-based tests. Levels of cervical fluid nitric oxide metabolite (NOx) were assessed by the Griess reaction. Main Outcome Measures. The difference in cervical fluid NOx between women with and without C. trachomatis and hrHPV. Results. Fourteen (67%) C. trachomatis-infected women and three (17%) noninfected women had concomitant hrHPV. The level of cervical fluid NOx in women with C. trachomatis (median 37.5μmol/l, 95% confidence interval 26.1-50.9) was higher ( p=0.02) than that in C. trachomatis-noninfected women (median 19.7μmol/L, 95% confidence interval 5.6-30.0). The presence of hrHPV did not associate with any difference in NOx levels between C. trachomatis-infected or -noninfected women. Conclusions. Chlamydia trachomatis was associated with increased release of nitric oxide metabolites in the uterine cervix. This stimulus was stronger than that of hrHPV, because no additional rise in NOx was seen in women with concomitant C. trachomatis and hrHPV infection. [ABSTRACT FROM AUTHOR]

The article discusses a study on the levels of cervical fluid nitric oxide metabolite (NOx) in women with or without high-risk (hr) human papillomavirus (HPV) and the value of which in the prediction of HPV persistence. The study involved women aged 18 to 64 years old in Finland. The study found that hr HPV persisted in 64% of the women and disappeared in 36%. Women with persistent hr HPV had higher median basal levels of NOx than those with eradicated hr HPV.

Hot flushes are complained of by approximately 75% of all postmenopausal women, and hormone therapy (HT) is the most effective way to alleviate them. Hot flushes are characterized by altered vascular function and sympathetic nervous system activity. Hot flushes occurred more often in women attending large, non-randomized observational studies (e.g. Nurses'' Health Study), where HT use protected against cardiovascular disease (CVD). However, they were absent (or mild) in randomized HT trials where HT use was accompanied with an elevated risk for CVD. Hot flushes, if a factor for cardiovascular health, could partly explain the conflict between observational and randomized trials. Several cross-sectional studies imply that hot flushes are detrimental to the cardiovascular system. However, the data are not uniform, and hot flushes were recalled retrospectively or during HT use. In our prospective study hot flushes were accompanied with a vasodilatory effect during endothelial testing, and this was related to the severity of hot flushes. Night-time hot flushes were followed with transient rises in ambulatory blood pressure (BP). However, no effect of hot flushes on diurnal BP was detected. The use of estradiol showed no harmful effects on endothelial function in women with hot flushes, but in non-flushing women oral, but not transdermal, estradiol led to vasoconstrictive changes. Estradiol complemented with medroxyprogesterone acetate eliminated the vasoconstrictive effect of sole oral estradiol. Thus, both oral and transdermal estradiol are applicable in flushing women, whereas a transdermal route should be favored in non-flushing women if used e.g. for bone protection. [ABSTRACT FROM AUTHOR]

Background. Blood pressure (BP) is one of the most powerful determinants of cardiovascular risk in women. This risk may differ between post-menopausal women with and without vasomotor hot flushes, possibly indicating different vascular responses to hormone therapy (HT). Thus, we compared in a clinical trial the effect of HT on ambulatory BP in normotensive, recently post-menopausal women with or without severe hot flushes. Methods. A total of 147 women recorded prospectively their hot flushes for 2 weeks; 70 women were symptomatic (≥7 moderate/severe hot flush episodes/day), whereas 77 women were defined as asymptomatic (≤3 mild hot flush episodes/day). Women were treated for 6 months with either transdermal estradiol, oral estradiol with or without medroxyprogesterone acetate, or placebo. Results. In symptomatic women decreases in BPs were seen during estradiol use. In contrast, in asymptomatic women receiving oral but not transdermal estradiol, increases in 24-h and day-time systolic and diastolic BPs were encountered. Conclusion. Hot flushes modify the HT-mediated responses in ambulatory BP. In asymptomatic women oral but not transdermal estradiol show potentially harmful cardiovascular effect by increasing BP. Our results give additional justification to prescribing HT primarily for the treatment of troublesome hot flushes and avoiding HT in women without vasomotor symptoms. [ABSTRACT FROM AUTHOR]

Background. Menopausal hot flushes may be a marker for a difference in vascular function. We studied the associations between hot flushes of varying severity and ambulatory blood pressure (BP) and heart rate (HR). Methods. A total of 147 women with onset of menopause within the preceding 6–36 months reported no hot flushes ( n = 23) or mild ( n = 33), moderate ( n = 30), or severe ( n = 61). Ambulatory BP and HR were registered for 24 hours. The variables, analyzed separately for day-time and night-time, were compared among the four study groups. Results. Hot flushes failed to show any relationship to mean day- or night-time BP, nocturnal dipping of BP, or HR. However, severe night-time hot flushes were accompanied by elevations in systolic BP (4.1 ± 10.5 mmHg, P = 0.061), diastolic BP (3.1 ± 6.8 mmHg, P = 0.032), and heart rate (3.0 ± 7.2 beats/minute, P = 0.043). Conclusion. Hot flushes are not associated with ambulatory BP or heart rate in normotensive, recently post-menopausal women, although severe night-time hot flush episodes are followed by significant elevations in BP and heart rate. The latter may be of clinical significance. [ABSTRACT FROM AUTHOR]

Objective. The human uterine cervix is capable of producing nitric oxide (NO). We studied the impact of cytological changes on the release of cervical NO. Design. Population-based case-control study. Setting. City of Helsinki, Finland. Population. Cervical cytology tests and cervical fluid samples were collected in 297 women. Methods. Cervical cytology tests, classified according to Bethesda criteria, were specifically analyzed for changes typically seen in human papillomavirus (HPV) infection, and the level of NO metabolites (NOx) in cervical fluid was assessed by Griess reaction. Main outcome measures. The difference in cervical fluid NOx between normal and abnormal cytology. Results. Cervical cytology was normal in 219 women and abnormal in 78 women. Among women with abnormal cytology there was both a higher detection rate (89% vs. 71%) and a higher concentration of NOx (median 22.5 µmol/l, 95% CI 14.6-31.9 vs. 11.0 µmol/l, 95% CI 8.0-16.7) compared to women with normal cytology. Age, parity, use of oral contraceptives, phase of the menstrual cycle, or history of miscarriage or termination of early pregnancy were not linked to an increased cervical NOx level. Conclusions. Cervical cell changes (suggestive of HPV infection) are accompanied by an increased release of NO in the human cervix. The significance of this finding remains uncertain, but in theory, increased release of NO could modify the outcome of cervical infection. [ABSTRACT FROM AUTHOR]

Abstract: Background: Vasoactive intestinal peptide (VIP) is a peptidergic neurotransmitter and a vasodilator with positive inotropic and chronotropic properties. Whether and how VIP contributes to the neuroendocrine response in heart failure (HF) is disputed, and there are no data on VIP in pressure overload-induced HF. Methods: We studied 129 adults with isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 48 patients, also from the coronary sinus for determination of VIP by radioimmunoassay. HF was diagnosed according to the European Society of Cardiology criteria. Results: Plasma VIP (mean±S.E.M.) was slightly higher in patients with HF (22.6±0.9 pmol/l, n =41) than in patients free of HF (21.1±0.5 pmol/l, n =88) or in 11 control patients without structural heart disease (20.0±1.3 pmol/l, n =11) (p =0.030 across the groups). VIP did not correlate with any measurement of cardiac structure or function in AS. The change in plasma VIP from aortic root to coronary sinus averaged +1.2±0.4 pmol/l in the 11 control patients (p =0.021), +1.2±0.2 pmol/l in 33 AS patients free of HF (p <0.001) and +0.8±0.3 pmol/l in 15 AS patients with HF (p =0.037). Conclusions: Both structurally normal and diseased hearts release VIP into the coronary sinus. Although marginally elevated in the systemic circulation, VIP is unlikely to contribute significantly to the neuroendocrine activation in HF due to pressure overload. [Copyright &y& Elsevier]

Abstract: Background: The pregnancy hormone relaxin has been raised as a new compensatory mediator of cardiac origin in heart failure (HF). We set out to assess the role of relaxin in pressure overload-induced human HF. Methods: We studied 129 adult patients undergoing cardiac catheterization for isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 49 patients, from the coronary sinus for the determination of plasma relaxin by enzyme immunoassay. HF was diagnosed when the patient had dyspnea or fatigue on ordinary effort in association with pulmonary wedge pressure >14 mm Hg at catheterization. Results: Forty-one patients had HF, which was systolic (ejection fraction <50%) in 16 patients and diastolic in 25 patients. The median plasma relaxin was 32 pg/ml (<12–297 pg/ml) in 88 AS patients without HF, 28 pg/ml (<12–825 pg/ml) in the 41 AS patients with HF, and 42 pg/ml (range, <12–100 pg/ml) in 11 control patients free of heart disease (p=0.82). Plasma relaxin did not correlate with any measurement of cardiac structure or function. The concentration gradients of relaxin from the aortic root to the coronary sinus indicated relaxin extraction by the heart in the control patients (median change, −5 pg/ml, p=0.038) vs. relaxin production in patients with systolic HF (median change, +6 pg/ml, p=0.028) (p=0.002 between groups). Conclusions: Although the heart may release relaxin into the circulation in certain forms of HF, this does not translate into elevated systemic concentrations. Relaxin is not a major player in human HF. [Copyright &y& Elsevier]

This review focuses on the question of whether the Women's Health Initiative (WHI) was a test of primary versus secondary cardiovascular benefits of postmenopausal hormone therapy. Evidence is presented to support the conclusion that the WHI was a secondary intervention trial and that primary cardiovascular benefits of hormone therapy are rational, likely, but not yet proven. The review makes clear that hormone therapy is not a 'cardiovascular drug' for the treatment of coronary heart disease; but rather that the public health debate is whether hormone therapy, used for the treatment of menopausal symptoms, provides any cardiovascular benefits that might offset its risk. [ABSTRACT FROM AUTHOR]

There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (>65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women or monkeys in the early stages of atherosclerosis progression has marked beneficial effects. Whether progestogens attenuate the cardiovascular benefits of estrogen replacement therapy has been controversial for more than a decade. Current evidence from studies of both monkeys and women suggest little or no attenuation of estrogen benefits for coronary artery atherosclerosis. Lack of compliance with estrogen replacement therapy, usually because of fear of breast cancer, remains a major problem. Future regimens may overcome that fear by the co-administration of a breast cancer preventive agent (i.e., selective estrogen receptor modulators, phytoestrogens) with low dose estrogen. [Copyright &y& Elsevier]