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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]

Abstract: Objective: Local cervical factors may determine the outcome of human papillomavirus (HPV) infection. Nitric oxide (NO) may be one such factor, since it is produced by uterine cervical cells and it takes part in both immunological and carcinogenic reactions. We studied the association between the presence of cervical high risk (hr) HPV DNA and NO in the cervical canal in women. Methods: High risk HPV DNA status was assessed from 328 women by using a specific DNA test and the release of cervical NO was assessed as nitrate/nitrite in cervical fluid. Cervical NO was then compared between women showing different status of hr HPV DNA and different cytological and histological findings. Results: High risk HPV DNA was present in 175/328 (53%) women. The cervical NO release in women with hr HPV DNA was 90% higher compared to hr HPV DNA negative women (p <0.001) (median 45.2 μmol/L; 95% CI 35.2–53.1 vs. 23.8 μmol/L; 95% CI 21.0–26.1). This elevation was not affected by parity, use of oral contraception, intrauterine devices, or signs of bacterial vaginosis or candida infection. Cytologically healthy epithelium and epithelium with mild cytological or histological changes showed elevated NO release if hr HPV DNA was present. Conclusions: The presence of hr HPV DNA is associated with an increased release of NO in the human uterine cervix. The clinical significance of this phenomenon remains open. [Copyright &y& Elsevier]

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]

• Estrone is the dominant adipose tissue estrogen in premenopausal women. • Estrone levels in adipose tissue are much higher than in the circulation. • Adipose tissue converts estrone sulfate to estrone, and estrone to estradiol. • Waist circumference correlates with higher estradiol production in subcutaneous fat. Although the ovaries produce the majority of estrogens in women before menopause, estrogen is also synthesized in peripheral tissues such as adipose tissue (AT). The typical female AT distribution, concentrated in subcutaneous and femoro-gluteal regions, is estrogen-mediated, but the significance of estrogen synthesis in AT of premenopausal women is poorly understood. Serum and subcutaneous and visceral AT homogenates from 28 premenopausal women undergoing non-malignant surgery were analyzed for estrone, estradiol, and serum estrone sulfate (E 1 S) concentrations with liquid chromatography-tandem mass spectrometry. Isotopic precursors were used to measure enzyme activities of estrone-producing steroid sulfatase and estradiol-producing 17 β -hydroxysteroid dehydrogenases (17 β -HSD). Messenger RNA (mRNA) expression levels of genes for estrogen-metabolizing enzymes were analyzed using real-time reverse transcription quantitative polymerase chain reaction. While estradiol was the predominant circulating active estrogen, estrone dominated in AT, with a higher concentration in visceral than subcutaneous AT (median, 2657 vs 1459 pmol/kg; P = 0.002). Both AT depots converted circulating E 1 S to estrone, and estrone to estradiol. Median levels of estrone were five to ten times higher in subcutaneous and visceral AT than in serum (P < 0.001) and the estradiol level in visceral AT was 1.3 times higher than in serum (P < 0.005). The local estrone concentration in visceral AT correlated positively with mRNA expression of estrone-producing enzyme aromatase (r = 0.65, P = 0.003). Waist circumference correlated positively with increased estradiol production in subcutaneous AT (r = 0.60, P = 0.039). Premenopausal AT demonstrated high estrogenic enzyme activity and considerable local estrogen concentrations. This may be a factor promoting female-typical AT distribution in premenopausal women. [ABSTRACT FROM AUTHOR]

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 (

Objective: Intrahepatic cholestasis of pregnancy predisposes women to liver disorders years after affected pregnancy. We compared the basal levels and responses of hyaluronic acid, a marker of liver fibrosis, and liver transaminases to postmenopausal hormone therapy in women with (n = 20) and without (n = 20) a history of intrahepatic cholestasis of pregnancy. Study Design: This was a randomized, double-blind, placebo-controlled, crossover trial. Results: Basal levels of hyaluronic acid were similar in both groups. Two weeks of oral estradiol 2.0 mg/day led to significant but similar (10.9% to 15.4%) rises in hyaluronic acid in both groups. Increasing the dose of oral estradiol to 4.0 mg/day resulted in normalization of the levels, whereas the addition of medroxyprogesterone acetate led to falls (11.0% to 10.7 %) in hyaluronic acid. Transdermal estradiol 50 μg led to a rise (3.2 %) in hyaluronic acid only in the control group. Other liver markers were normal at baseline and during hormone therapy. Conclusion: Normal basal levels and/or normal responses of hyaluronic acid and other liver markers to hormone therapy in women with previous intrahepatic cholestasis suggest that this therapy does not predispose these women to liver diseases. [Copyright &y& Elsevier]

Objectives: Many in vitro fertilization (IVF) complications are inflammatory by nature, some of which are even life-threatening. We evaluated the response of C-reactive protein (CRP) in IVF complications, especially in early and late ovarian hyperstimulation syndrome (OHSS), to support clinical decision making in gynecological emergency policlinics.Study Design: In a prospective two-year study at Helsinki University Hospital, Finland, we recruited patients with IVF complications including moderate or severe OHSS (n=47 patients: 36 early and 14 late OHSS cases), or other IVF complications (n=13). As controls, we recruited women in an uncomplicated IVF cycle (n=27). Serial blood samples (CRP, blood count, platelets, albumin, estradiol, creatinine, and electrolytes) were collected from patients upon admission to the emergency polyclinic and during and after treatment on the ward, and from the controls prior, during, and after the IVF protocol. All samples were categorized according to oocyte pick-up (OPU). The statistics included comparisons between and within the study groups, and receiver-operating characteristic (ROC) curve analysis for diagnostic accuracy of CRP for early OHSS at emergency polyclinics.Results: On admission, CRP did not differentiate OHSS from other IVF complications, but CRP was higher in early (median 21; IQR 8-33mg/L) than in late (6; 3-9mg/L, p=0.001) OHSS. In ROC analysis for CRP (12mg/L), the area under the curve (AUC) was 0.74 (p=0.001) with sensitivity of 69% and specificity of 71% for early OHSS. CRP was significantly higher (28; 10-46mg/L) in patients with early OHSS two days after oocyte pick-up (OPU) than in the controls (5; <3-9mg/L, p<0.001). The level normalized by 12 days, similarly to the controls. On the ward, the peak CRP was higher if early OHSS was complicated with infection (108; 49-166mg/L) than without infection (20; 8-32mg/L, p=0.001). Late OHSS was associated with hypoalbuminemia (19.6; 16.2-23.1g/L, p<0.001) and thrombocytosis (494; 427-561 E9/L, p=0.004; comparisons to early OHSS).Conclusions: Early OHSS associates with a distinct rise in CRP level beyond that induced by uncomplicated oocyte pick-up, whereas the CRP levels in late OHSS are comparable to those in the control cycles. CRP identifies, but cannot distinguish IVF complications. [ABSTRACT FROM AUTHOR]

• Hormone therapy decreased cardiovascular disease risk in women with prior pre-eclampsia. • Ten years of hormone therapy reduced cardiovascular events with 5-8 in 1000 pre-eclamptic women. • Menopausal women with a history of pre-eclampsia should receive this information. Women with prior pre-eclampsia are at increased risk of cardiovascular disease (CVD). Menopausal hormone therapy (MHT) may affect this risk. We evaluated the impact of MHT use on cardiovascular risk between women with and without prior pre-eclampsia. We assessed the occurrence of any CVD, myocardial infarction (MI) and stroke in MHT users (n = 9700) and non-users (n = 19,914) with prior pre-eclampsia, and likewise in MHT users (n = 27,764) and non-users (n = 58,248) without prior pre-eclampsia over the period 1994–2019. Follow-up started at MHT initiation (mean age 50.4 in pre-eclamptic women and 50.3 in non-pre-eclamptic women) and lasted for a mean of 13.3 years. The use of MHT in prior pre-eclamptic women was associated with significant risk reductions for any CVD (HR 0.85, 95 % CI 0.78–0.91), MI (HR 0.66, 95 % CI 0.55–0.78) and stroke events (HR 0.71, 95 % CI 0.63–0.81) in comparison with non-users with prior pre-eclampsia. The risk reductions for cardiovascular deaths were even more pronounced (HR 0.43, 95 % CI 0.31–0.59 for any CVD death; HR 0.49, 95 % CI 0.30–0.80 for MI death; HR 0.25, 95 % CI 0.10–0.64 for stroke death). However, none of these risk reductions differed from those seen in MHT users without prior pre-eclampsia. The risk of any CVD decreased already within five years of MHT use in women with prior pre-eclampsia but not in those without prior pre-eclampsia. The use of MHT is associated with reduced CVD risk in women with prior pre-eclampsia. This is important to clinicians considering the initiation of MHT for recently menopausal women with prior pre-eclampsia. [ABSTRACT FROM AUTHOR]

Purpose: Hysterectomy and mid-urethral sling (MUS) are common operations, but little is known about how hysterectomy after MUS affects the risk for stress urinary incontinence (SUI) relapse.Methods: We included 49 women with a MUS before hysterectomy and 41 women with a MUS concomitant with hysterectomy. The controls, matched by age (± 2 years), MUS type (retropubic vs transobturator) and operation year (± 2 years), included 201 women who underwent the MUS operation without a subsequent hysterectomy. We used health care registers for follow-up of 12.4 years in median (IQR 10.9-14.7) after the MUS operation to compare the number of SUI re-operations and hospital re-visits for urinary incontinence.Results: The re-operation rates for SUI did not differ between the women with MUS before hysterectomy (n = 2, 4.1%), women with MUS concomitant with hysterectomy (n = 2, 4.9%) and their controls (n = 4, 4.9%, p = 0.8 and n = 6, 5.0%, p = 1.0, respectively). There were significantly fewer urinary incontinence re-visits among women who had a MUS concomitant with the hysterectomy compared to their matched controls (n = 2 and 31, 5 and 31%, p < 0.01) and to the women with a MUS prior to hysterectomy (n = 2 and 10, 5 and 20%, respectively, p = 0.03).Conclusion: Hysterectomy after or concomitant with MUS does not seem to increase the risk for SUI re-operation or hospital re-visits for urinary incontinence. These results can be used to counsel women considering hysterectomy after MUS operation or concomitant with MUS operation. [ABSTRACT FROM AUTHOR]

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]

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]

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 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]

Purpose: The aim of this study was to compare long-term effects of high-volume surgery at a single-center to multicenter use when using a mesh-capturing device for pelvic organ prolapse (POP) repair. Methods: Five years after surgery 101 (88%) at the single center were compared with 164 (81.2%) in the multicenter trial. Outcome measurements included clinical examination, prolapse-specific symptom questionnaires [Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire—short form (PFIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12)] and pain estimation by VAS (0–10). Results: Optimal apical segment outcome was 95% in the single- compared to 83.3% in the multicenter study (p < 0.001). POP recurrence in the anterior and posterior walls (POP-Q, Ba and Bp ≥ 0) was more common at the multicenter as compared to the single center [(19.8% vs 5.4%) and (26% vs 2.7%), (p < 0.001)]. Reoperations for POP and mesh-related complications were more frequent in the multicenter study [31/202 (15.3%) vs 7/116 (6.1%), p < 0.001]. Total PFDI-20, PFIQ-7 and PISQ-12 scores were comparable between the cohorts. There were no significant differences in overall pain scores in-between the cohorts during follow-up. At the single center, 1/81 patients (1.2%) had VAS 7/10, i.e. severe pain, as compared to 3/131 (2.3%) in the multicenter study (p = 0.277). Conclusions: Despite the high objective and subjective long-term effectiveness of the procedure in both regular use, and at a high-volume center, centralizing the use of a standardized capturing-device guided transvaginal mesh for POP repair reduced secondary interventions by more than half. [ABSTRACT FROM AUTHOR]

Purpose: Pentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF).Methods: This two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC).Results: The circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15-20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level.Conclusion: The elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS. [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]

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]

Highlights • Heavier women had lower serum DHEA, DHT and SHBG compared to their leaner co-twins. • Serum DHEA concentration was best predicted by percent body fat within twin pairs. • Insulin resistance did not explain serum androgen or SHBG levels within twin pairs. • STS and AKR1C genes were more expressed in adipose tissue from the heavier women. • Intra-abdominal fat and leptin were important regarding adipocyte expression of STS. Abstract Objective Obesity may alter serum steroid concentrations and metabolism. We investigated this in healthy young women with increased body fat and their leaner co-twin sisters. Design Age and genetic background both strongly influence serum steroid levels and body composition. This is a cross-sectional study of 13 female monozygotic twin pairs (age, 23–36 years), ten of which were discordant for body mass index (median difference in body weight between the co-twins, 19 kg). Methods We determined body composition by dual energy X-ray absorptiometry and magnetic resonance imaging, serum androgens by liquid chromatography-tandem mass spectrometry, and mRNA expression of genes in subcutaneous adipose tissue and adipocytes. Results The heavier women had lower serum dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) (P < 0.05 for all) compared to their leaner co-twins with no differences in serum testosterone or androstenedione levels. Serum DHEA correlated inversely with %body fat (r = −0.905, P = 0.002), and DHT positively with SHBG (r = 0.842, P = 0.002). In adipose tissue or adipocytes, expressions of STS (steroid sulfatase) and androgen-related genes were significantly higher in the heavier compared to the leaner co-twin, and within pairs, correlated positively with adiposity but were not related to serum androgen levels. None of the serum androgen or SHBG levels correlated with indices of insulin resistance. Conclusions Serum DHEA levels were best predicted by %body fat, and serum DHT by SHBG. These or other serum androgen concentrations did not reflect differences in androgen-related genes in adipose tissue. General or intra-abdominal adiposity were not associated with increased androgenicity in young women. [ABSTRACT FROM AUTHOR]

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n = 18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22–36 kg/m 2 ] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3 kg/m 2 ]. Sex steroid concentrations were determined by liquid chromatography–tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI = 5.9 kg/m 2 ), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs . 2.4 (1.0) nmol/l, P = 0.040] and mRNA expressions of DHT-inactivating AKR1C2 ( P = 0.021) and cortisol-producing HSD11B1 ( P = 0.008) higher in the heavier compared to the leaner co-twins. Serum free 17 β -estradiol (E2) was higher [2.3 (0.5) vs . 1.9 (0.5) pmol/l, P = 0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs . 90 (22) pmol/l, P = 0.006; and 123 (43) vs . 105 (27) pmol/l, P = 0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations ( P < 0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG ( P < 0.05), and 3) liver fat with SHBG ( P = 0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2 , HSD11B1 , and aromatase in adipose tissue ( P < 0.05). In conclusion, acquired adiposity was associated with decreased serum DHT and increased estrogen concentrations, independent of genetic factors and age. The reduction of DHT could be linked to its increased degradation (by AKR1C2 and HSD11B1) and increased estrogen levels to increased adiposity-related expression of aromatase in adipose tissue. [ABSTRACT FROM AUTHOR]

Objective: To study the effects on quality of life in women operated for apical pelvic organ prolapse using the Vaginal Uphold™ System.Study Design: In this prospective cohort study, women (n=207) with symptomatic apical prolapse, with or without cystocele, were operated using the Uphold™ Vaginal Support System. Follow-up for quality of life was performed at 12 months after surgery, and assessed by the PFDI-20, and PFIQ-7, and sexual function by the PISQ-12. We used odds ratios (ORs) with 95% confidence intervals (CIs) for outcome association analyses using logistic regression.Results: At one-year follow-up majority of women experienced an overall postoperative improvement in quality of life (p<0.001). One year after surgery Uphold™ operation alone increased the risk for prolapse related bother as compared to Uphold™ combined with anterior colporraphy (POP-IQ-7; OR 2.1; 95% CI 1.01-4.3). The frequency of dyspareunia decreased postoperatively (p=0.004), however, after one-year, overall sexual function deteriorated significantly (p<0.001). The worsening in sexual function scores was mainly attributed to the partner related domain, whereas the behavioral-emotive and physical domains showed no significant changes.Conclusion: Apical prolapse repair using Uphold™ improved quality of life among our patients but worsened overall sexual function postoperatively. [ABSTRACT FROM AUTHOR]

Estrone is the most abundant estrogen after the menopause. We developed a liquid chromatography-tandem mass spectrometric method (LC–MS/MS) for determination of estrone in adipose tissue. Subcutaneous adipose tissue from the breast was collected during elective surgery in postmenopausal women undergoing mastectomy for treatment of breast cancer ( n = 13) or reduction mammoplasty (controls, n = 11). Homogenized adipose tissue was extracted with organic solvents and the estrone fraction was purified by LH-20 column chromatography from the excess of lipids. The concentration of estrone was analyzed by LC–MS/MS. The method was accurate with an intra-assay variation of 8% and an interassay variation of 10%. The median concentration of estrone in subcutaneous adipose tissue from the breast did not differ between breast cancer and control women, 920 pmol/kg and 890 pmol/kg, respectively. In breast cancer patients but not in the controls, breast adipose tissue estrone levels correlated positively with the serum estrone concentration. In conclusion, the new method provides a reliable means to measure estrone concentrations in adipose tissue in postmenopausal women. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess whether coronary heart ahhdisease mortality in Finnish hormone therapy (HT) users differed before and after 2002 when the Women's Health Initiative study was published. METHODS: The risks of coronary heart disease death in HT users in relation to the age-matched background population were compared between the pre- (1995-2001) and post- (2002-2009) Women's Health Initiative eras. We used a nationwide register on HT (ie, estradiol with or without progestin) reimbursement and linked them to causes of death in 290,272 women aged 40 years or older. RESULTS: Exposure to HT for 1 year or less was accompanied by a 29% reduction (0.71; 0.63-0.80; three per 10,000 fewer deaths) and an exposure of 1-8 years with a 43% reduction (0.57; 0.48-0.66; three per 10,000 fewer deaths) in the risk of coronary heart disease death in the pre-Women's Health Initiative era. In the post- Women's Health Initiative era, HT use of 1 year or less was associated with an 18% reduction (0.82; 0.76-1.00; one per 10,000 fewer deaths) and an exposure of 1-8 years with a 54% reduction (0.46; 0.32-0.64; two per 10.0 fewer deaths) in coronary heart disease mortality. Discontinuation of HT was associated with an increased risk of cardiac death of 42% (1.42; 1.17-1.71; seven per 10.0 extra deaths) in the pre-Women's Health Initiative era and 31% (1.31; 0.92-1.82; two per 10,000 extra deaths) in the post-Women's Health Initiative era during the first posttreatment year. This risk increase vanished in further follow-up during both eras. CONCLUSION: Changes in HT use after the Women's Health Initiative failed to affect coronary heart disease mortality of HT users in this nationwide study. [ABSTRACT FROM AUTHOR]

Abstract: Background: Menopause is associated with poor sleep quality and daytime sleepiness, which may lead to impaired quality of life and impaired functioning in daily activities. Objective: To study whether exercise training improves sleep quality or decreases the amount of night time hot flushes among menopausal women with vasomotor symptoms. Study design: A randomized controlled trial. Sedentary women (N =176) aged 43–63 years with menopausal symptoms were randomized to a six-month unsupervised aerobic training intervention (50min 4 times per week) or a control group. Both groups attended lectures on physical activity and health once a month. Main outcome measures: Sleep quality and the amount of hot flushes disturbing sleep. The women reported daily via mobile phone whether hot flushes had disturbed their sleep and how they had slept (scale 1–5). Responses received by mobile phone over the 6-month period totaled on average 125 (5.2 per week) responses per participant. Results: At baseline there was no difference between the groups in the demographic variables. Sleep quality improved significantly more in the intervention group than in the control group (OR 1.02; 95% CI=1.0–1.05, p =0.043). The odds for sleep improvement were 2% per week in the intervention group and a decrease of 0.5% per week in the control group. The amount of hot flushes related to sleep diminished (p =0.004) by the end of the intervention. Conclusions: Aerobic training for 6 months may improve sleep quality and reduce hot flushes among symptomatic menopausal women. [Copyright &y& Elsevier]

Abstract: Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) are naturally occurring water-insoluble metabolites of DHEA, which are transported in plasma exclusively by lipoproteins. To find out whether DHEA, like estradiol, might be stored in adipose tissue in FAE form, we set up a mass spectrometric method to quantify DHEA-FAE and free DHEA in human adipose tissue and serum. The method consists of chromatographic purification steps and final determination of hydrolyzed DHEA-FAE and free DHEA, which was carried out by gas chromatography–mass spectrometry (GC–MS) or liquid chromatography–tandem mass spectrometry (LC–MS/MS). Our results showed that no detectable amounts of DHEA-FAE could be found in adipose tissue although 32–178pmol/g of free DHEA were determined by GC–MS and LC–MS/MS. The DHEA-FAE concentrations in serum quantified by GC–MS were 1.4±0.7pmol/ml in premenopausal women (n =7), and 0.9±0.4pmol/ml in postmenopausal women (n =5). Correspondingly, the free DHEA concentrations were 15.2±6.3pmol/ml and 6.8±3.0pmol/ml. In addition, the mean proportions of DHEA-FAE of total DHEA (DHEA-FAE+free DHEA) in serum were 8.6% and 11.2% in pre- and postmenopausal women, respectively. Serum DHEA-FAE concentration was below quantification limit for LC–MS/MS (signal-to-noise ratio, S/N =10), while free DHEA concentrations varied between 5.8 and 23.2pmol/ml. In conclusion, the proportion of DHEA-FAE of total DHEA in serum was approximately 9%. However, in contrast to our previous findings for estradiol fatty acid esters in adipose tissue which constituted about 80% of total estradiol (esterified+free), the proportion of DHEA-FAE of total DHEA was below 5%. Four to ten times higher concentrations of free DHEA were quantified in adipose tissue compared to those in serum. [Copyright &y& Elsevier]

Abstract: Objective: Equol, a gut bacterial metabolite of isoflavone daidzein, may improve health through changes in vascular function and in estrogen metabolism. Tibolone, a synthetic steroid alternative for the treatment of postmenopausal symptoms, causes a different estrogenic milieu than estrogen and may affect vascular health. We studied the effects of equol production and soy supplementation on vascular function in postmenopausal women under long-term tibolone use. Methods: We screened 110 women using tibolone for 3–60 months for high equol production capacity with a one-week soy challenge. Twenty women with high equol production capacity (4-fold elevation in equol level) and 20 comparable control women without this capacity were treated in a randomized placebo-controlled cross-over trial with a soy drink (52g of soy protein containing 112mg of isoflavones) or placebo for 8 weeks. Arterial stiffness and endothelial function were assessed before and after soy and placebo supplementation with pulse-wave analysis. Results: Prior to soy supplementation arterial stiffness, expressed as augmentation index, was lower (p =0.01) in equol producers (25.9±1.1%) than non-equol producers (29.6±0.9%). Similarly, endothelial function index was better at baseline (p =0.009) in these women (72.3±5.3%) compared to women lacking equol production capacity (55.2±3.8%). Soy supplementation had no effect on arterial stiffness or endothelial function in either group. Conclusion: In postmenopausal tibolone users, endogenous equol production capability is associated with favorable vascular function. This phenomenon was not affected by soy and thus, equol producing capacity may be an independent vascular health marker, at least in postmenopausal women using tibolone. [Copyright &y& Elsevier]

MicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation and lipid metabolism are uncharacterized. miR-221-3p or its inhibitor was transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1 , GLUT4 , FAS , DGAT1/2 , AP2 , ATGL and AdipoQ, whereas the miR-221-3p inhibitor increased TG storage. Knockdown of the predicted miR-221-3p target, 14-3-3γ, had similar antiadipogenic effects as miR-221-3p overexpression, indicating it as a potential mediator of mir-221-3p function. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression. • miR-221-3p suppresses adipogenesis, putatively mediated by 14-3-3γ downregulation. • miR-221-3p suppresses de novo lipogenesis in adipocytes. • miR-221-3p alters adipocyte ceramide, sphingomyelin and diacylglycerol content. • miR-221-3p expression is elevated in adipocytes adjacent to breast carcinoma. • Adipocyte miR-221-3p elevation may promote metabolic disease and cancer progression. [ABSTRACT FROM AUTHOR]

Context: Women with a history of pre-eclamptic pregnancy are predisposed to later occlusive vascular diseases., Objective: We compared the use of cyclic progestins or levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of menstrual cycle abnormalities between premenopausal women with and without a prior pre-eclamptic pregnancy., Setting and Participants: Register-based cohort study during 1994-2019 of oral progestin or levonorgestrel-releasing intrauterine device (LNG-IUD) in Finnish women with (n=31 688) and without (n=91 726) prior pre-eclampsia in 1969-1993., Main Outcome Measures: Cyclic progestin or LNG-IUD use and its association with future use of menopausal hormone therapy (MHT)., Results: Prior pre-eclamptic women had used cyclic progestins more often (23.5% vs. 9.1%; p<0.001) and initiated the use at younger ages (41.8 years [SD=6.3] vs. 45.9 years [3.1]; p<0.001) than control women. Also, LNG-IUD was inserted more frequently (p<0.001) in prior pre-eclamptic women (9.3%) than in controls (4.7%). Cyclic progestin or LNG-IUD use was accompanied by significant 37-90% elevations in future MHT use., Conclusions: Increased use of cyclic progestins and LNG-IUD in premenopausal women with a history of pre-eclamptic pregnancy can be seen as indirect evidence of earlier onset of ovulatory dysfunction. This may contribute to the elevated risk of endometrial cancer in these women. Our findings may indicate one additional late sequela of pre-eclamptic pregnancy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Context: The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized., Objective: We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women., Design, Setting, Patients, and Interventions: Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n=50) and without (n=13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction., Results: HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to non-users. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to non-users of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users., Conclusions: Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT, and these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To study the effect of the childbirth experience on the likelihood and interval to a subsequent live birth., Design: Retrospective analysis of a 7-year cohort., Setting: Childbirths in Helsinki University Hospital delivery units., Participants: All parturients giving birth to a term and living baby from a single pregnancy in Helsinki University Hospital delivery units from January 2012 to December 2018 (n=120 437). Parturients delivering their first child (n=45 947) were followed until the birth of a subsequent child or the end of 2018., Main Outcome Measure: The interval to a subsequent childbirth connected to the experience of the first childbirth was the primary outcome of the study., Results: A negative first childbirth experience decreases the likelihood of delivering a subsequent child during the follow-up (adjusted HR=0.81, 95% CI 0.76 to 0.86) compared with those experiencing the first childbirth as positive. For parturients with a positive childbirth experience, the median interval to a subsequent delivery was 3.90 years (3.84-3.97) compared with 5.29 years (4.86-5.97) after a negative childbirth experience., Conclusion: The negative childbirth experience influences reproductive decisions. Consequently, more focus should be placed on understanding and managing the antecedents of positive/negative childbirth experiences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the impact of pre-eclampsia on the future cardiovascular risk in Finnish women DESIGN: A registry-based nationwide controlled cohort study., Setting: Women hospitalised for pre-eclampsia in 1969-1993 and control women with a history of normotensive pregnancies followed from the pre-eclampsia diagnosis until 2019 for cardiovascular outcomes., Participants: 31 688 women with and 91 726 control women without a history of pre-eclampsia., Primary Outcome Measures: Incidences of and deaths from ischaemic heart disease (IHD), myocardial infarction (MI) and stroke., Results: In total, 25 813 (81.5%) women had pre-eclampsia without severe features, 4867 (15.4%) had pre-eclampsia with severe features and 1006 (3.2%) women developed eclampsia. Women with a history of pre-eclampsia showed elevated risks for IHD (HR 1.52, 95% CI 1.44 to 1.59), MI (HR 1.66, 95% CI 1.52 to 1.81) and stroke (HR 1.40, 95% CI 1.32 to 1.48). The risks for death from IHD (HR 1.50, 95% CI 1.28 to 1.75), MI (1.63, 95% CI 1.30 to 2.05) and stroke (1.44, 95% CI 1.03 to 2.01) were also elevated. Pre-eclampsia with severe features or eclampsia was accompanied with 15% higher IHD risk, 19% higher MI risk and 26% higher stroke risk than pre-eclampsia without severe features. The highest risk elevations of 30% for IHD, 32% for MI and 30% for stroke were observed in women with recurrent pre-eclampsia (n=4180)., Conclusion: Pre-eclampsia-related significant elevations in CVD risks of Finnish women with inherently high risk for these diseases were of the same magnitude as reported previously from other countries. Thus, women with a history of pre-eclampsia should be screened and treated early for modifiable cardiovascular risk factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We sought to determine whether polyacrylamide hydrogel (PAHG) is noninferior to tension-free vaginal tape (TVT) in the treatment of women with primary stress urinary incontinence (SUI)., Materials and Methods: In this noninferiority trial, 223 women eligible for operative SUI treatment were randomized for TVT (110) or PAHG (113). Primary outcome was patient satisfaction and the noninferiority margin for the difference was 20%. Secondary outcomes were effectiveness and complications., Results: At 3 years, 188 (84.3%) women attended the followup. The satisfaction score (visual analogue scale 0-100) median was 98.5 (IQR 90-100) in the TVT group and 90.0 (IQR 70-100) in the PAHG group, whereas a score ≥80 was reached in 87 (94.6%) and 65 (67.7%), respectively (difference 26.9%, 95% CI 16.7% to 36.8%). Thus, PAHG did not meet the noninferiority criteria set in our study. The cough stress test was negative in 88 (95.7%) of TVT patients vs 75 (78.1%) of PAHG patients (difference 17.5%, 95% CI 8.6% to 26.9%). Any peri- or postoperative complication before crossover between the groups was detected in 40 (43.5%) women in the TVT group and 23 (24.0%) women in the PAHG group (difference 19.5%, 95% CI 6.8% to 31.4%)., Conclusions: In midterm followup, PAHG did not reach in patient satisfaction the noninferiority set in our study. Furthermore, mid urethral TVT slings show better subjective and objective cure rates than PAHG. However, complications were more often associated with TVT. Since the majority of PAHG treated women were also cured or improved, primary SUI women can be offered PAHG as a safe and durable alternative treatment.