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Objective: 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., Study Design and Main Outcome Measures: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest MV, JJ, MG and OY have nothing to declare. HSP has been a member of the advisory board of Ferring Pharmaceuticals and a consultant to Astellas, Merck and Orion. TM received consulting fees from Abbott, Astellas, Viatris and Orion., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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.)

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., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

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: 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: 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., (© 2022. The Author(s).)

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.

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.

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 (mean PRIMI =8.00 [95% CI 7.96-8.04], mean MULTI =8.50 [8.47-8.53]) was perceived more positive than operational deliveries with spontaneous labour (means PRIMI ≤7.66 [7.61-7.70], means MULTI ≤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., (© 2022. The Author(s).)

Objectives: The aim of this study was to analyse the relation between the used labour pain relief and childbirth experience measured by Visual Analogue Scale (VAS)., Design: A retrospective cohort study., Setting: Childbirth in five Helsinki University Hospital delivery units from 2012 to 2018., Primary Outcome Measure: Childbirth experience measured by VAS and classified in three groups (negative VAS=1-5, positive VAS=6-8 and highly positive=9-10)., Results: The use of epidural or non-epidural compared with non-medical pain relief methods decreased the likelihood to experience highly positive childbirth for primiparous (adjusted OR (aOR) EPIDURAL =0.64, 95% CI 0.57 to 0.73; and aOR NON-EPIDURAL =0.76, 95% CI 0.66 to 0.87) and multiparous (aOR EPIDURAL =0.90, 95% CI 0.84 to 0.97 and aOR NON-EPIDURAL =0.80, 95% CI 0.74 to 0.86) parturients. The effects of epidural differed between primiparas and multiparas. In multiparas epidural was associated with decreased odds for experiencing negative childbirth compared with the non-medical group (aOR=0.70, 95% CI 0.57 to 0.87), while the effect of epidural was considered insignificant in primiparas (aOR=1.28, 95% CI 0.93 to 1.77)., Conclusion: While the use of medical-epidural and non-epidural-pain relief methods were not associated with odds for experiencing negative childbirth in primiparas, using epidural helps to avoid negative experience in multiparas. However, the odds for experiencing highly positive childbirth were decreased if the parturients used any medical pain relief for both primiparas and multiparas. Consequently, the effect of pain relief on the childbirth experience is strongly confounded by indication. Thus, the use of pain relief per se plays a limited role in the complex formation of the overall childbirth experience., 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.)

Direct ink writing via single or multihead extrusion is used to synthesize layer-by-layer (LbL) meshes comprising renewable polysaccharides. The best mechanical performance (683 ± 63 MPa modulus and 2.5 ± 0.4 MPa tensile strength) is observed for 3D printed structures with full infill density, given the role of electrostatic complexation between the oppositely charged components (chitosan and cellulose nanofibrils). The LbL structures develop an unexpectedly high wet stability that undergoes gradual weight loss at neutral and slightly acidic pH. The excellent biocompatibility and noncytotoxicity toward human monocyte/macrophages and controllable shrinkage upon solvent exchange make the cellular meshes appropriate for use as biomedical implants., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Objectives: To explore how the time of delivery influences childbirth experience., Design: A retrospective cohort study., Setting: Childbirth in the four Helsinki and Uusimaa Hospital District hospitals, Finland, from 2012 to 2018., Participants: 105 847 childbirths with a singleton live fetus., Main Outcome Measures: Childbirth experience measured by Visual Analogue Scale (VAS)., Results: The major difference in average childbirth experience measured by VAS was between primiparas (8.03; 95% CI 8.01 to 8.04) and multiparas (8.47; 95% CI 8.45 to 8.48). Risk ratio (RR) of the low VAS (≤5) was 2.3 when primiparas were compared with multiparas. Differences in VAS between distinct periods were found in two stages: annual and time of day. The decrease in VAS from 2012-2016 to 2017-2018 in primiparas was from 7.97 (95% CI 7.95 to 7.99) to 7.80 (95% CI 7.77 to 7.83) and from 2014-2016 to 2017-2018 in multiparas from 8.60 (95% CI 8.58 to 8.61) to 8.49 (95% CI 8.47 to 8.52). Corresponding RRs of low VAS were 1.3 for primiparas and 1.2 for multiparas. Hourly differences in VAS were detected in primiparas between office hours 08:00-15:59 (7.97; 95% CI 7.94 to 7.99) and other times (night 00:00-07:59; 7.91; 95% CI 7.88 to 7.94; and evening 16:00-23:59; 7.90; 95% CI 7.87 to 7.92). In multiparas differences in VAS were detected between evening (8.52; 95% CI 8.50 to 8.54) and other periods (night; 8.56; 95% CI 8.54 to 9.58; and office hours; 8.57; 95% CI 8.55 to 8.59)., Conclusion: The maternal childbirth experience depended on the time of delivery. Giving birth during the evening led to impaired childbirth experience in both primiparas and multiparas, compared with delivery at other times. The impact of labour induction on childbirth experience should be further examined. The reorganisation of delivery services and the reduction of birth preparations might affect annual VAS. VAS is a simple method of measuring the complex entity of childbirth experience, and our results indicate its ability to capture temporal variation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: 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., Design and Methods: 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 17β-hydroxysteroid dehydrogenases (17β-HSD). Messenger RNA (mRNA) expression levels of genes for estrogen-metabolizing enzymes were analyzed using real-time reverse transcription quantitative polymerase chain reaction., Results: 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)., Conclusions: 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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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.

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.

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.

Purpose: We evaluated whether polyacrylamide hydrogel is noninferior to tension-free vaginal tape to treat women with primary stress urinary incontinence., Materials and Methods: In this controlled noninferiority clinical trial patients with primary stress urinary incontinence were randomized to tension-free vaginal tape or polyacrylamide hydrogel treatment. The primary outcome was patient satisfaction and secondary outcomes were effectiveness in reducing urinary leakage and complications at 1-year followup. For statistical power significance was considered at 5%, power was set at 80% and the noninferiority limit was 20% with a 10% expected dropout rate., Results: A total of 224 women with primary stress urinary incontinence entered the study between September 28, 2015 and March 1, 2017. Of the women 111 were randomized to tension-free vaginal tape and 113 were randomized to polyacrylamide hydrogel. At 1 year a satisfaction score of 80 or greater on a visual analogue scale of 0 to 100 was reached in 95.0% and 59.8% of patients treated with tension-free vaginal tape and polyacrylamide hydrogel, respectively. Thus, polyacrylamide hydrogel did not meet the noninferiority criteria set in our study. As secondary outcomes, the cough stress test was negative in 95.0% of tension-free vaginal tape cases vs 66.4% of polyacrylamide hydrogel cases (difference 28.6%, 95% CI 18.4-38.5). However, most perioperative complications, including those in 19 tension-free vaginal tape cases vs 3 polyacrylamide hydrogel cases (difference 16.0%, 95% CI 7.8-24.9), and all 6 reoperations due to complications (difference 5.9%, 95% CI 1.2-12.4) were associated with tension-free vaginal tape., Conclusions: Mid urethral tension-free vaginal tape slings were associated with better satisfaction and cure rates than polyacrylamide hydrogel in women with primary stress urinary incontinence. However, complications were mainly associated with tension-free vaginal tape. Thus, tension-free vaginal tape should be offered as first line treatment in women who expect to be completely cured by the initial treatment and are willing to accept the complication risks. Since polyacrylamide hydrogel treatment also provides high satisfaction and cure rates, women with primary stress urinary incontinence can be offered polyacrylamide hydrogel as an alternative treatment.

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.

Objective: This study aimed to assess the long-term (5 years) outcomes of the Uphold Vaginal Support System for symptomatic vaginal apical prolapse with or without anterior colporraphy., Methods: In total, 164 (81.2%) of 202 women operated on in 24 centers were reached for follow-up. Outcomes were assessed by using the Pelvic Organ Prolapse Quantification, the Pelvic Floor Distress Inventory 20, and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire questionnaires. Pain on pelvic area was evaluated using a visual analog scale. Adverse events and secondary procedures were recorded., Results: An optimal outcome at the apical compartment (Pelvic Organ Prolapse Quantification stage <2) was achieved in 83.3% of patients (94% at 1 year). Quality of life improved in 78.8% of the women, with a significant decrease of bother in all domains (pelvic organ prolapse, rectoanal, urinary) compared with that preoperatively. Overall sexual satisfaction improved after 1 year, but the number of sexually active women was low. In total, 19.7% of patients had undergone repeat pelvic surgery during follow-up, most common of these were midurethral sling (38.4%), followed by prolapse-related operations. Mesh removal due to pain was performed in 3 women. Number of women with any pain decreased overall from 1 to 5 years, but 3 women had persistent severe pain despite treatment efforts (visual analog scale ≥7)., Conclusions: Apical objective and subjective outcomes were sustained after 5 years in women operated on for apical compartment prolapse by the Uphold Vaginal Support System.

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.

Purpose: Mirabegron, a β 3 -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., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Objective: Receptors for estrogen and progesterone are present in the pelvic floor, and therefore, postmenopausal hormone therapy may affect its function. We compared the former use of estradiol-progestogen postmenopausal hormone therapy in nonhysterectomized women with a uterine prolapse surgery (N = 12,072) and control women (N = 33,704)., Methods: The women with a history of uterine prolapse operation were identified from the Finnish National Hospital Discharge Register, and the control women from the Finnish Central Population Register. The use of hormone therapy was traced from the national drug reimbursement register, and the odd ratios with 95% CIs for prolapse were calculated by using the conditional logistic regression analysis., Results: The women with uterine prolapse had used hormone therapy more often than control women (N = 4,127; 34.2% vs N = 9,189; 27.3%; P < 0.005). The use of hormone therapy was accompanied by significant (23%-53%) elevations in the risk for prolapse, being higher with longer exposure. The risk elevations (33%-23%) were comparable between sole norethisteroneacetate-estradiol and sole medroxyprogesteroneacetate-estradiol therapy. The use of estradiol in combination with a levonorgestrel releasing intrauterine device was accompanied by a 52% elevation., Conclusions: The postmenopausal use of estradiol in combination with various progestogen regimens may weaken the pelvic floor, resulting in uterine prolapse. This data should be incorporated into the information given to the users of estradiol-progestogen hormone therapy.

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.

Circulating estrogens fluctuate during the menstrual cycle but it is not known whether this fluctuation is related to local hormone levels in adipose tissue. We analyzed estrogen concentrations and gene expression of estrogen-regulating enzymes in breast subcutaneous adipose tissue in premenopausal women with (n = 11) and without (n = 17) estrogen receptor-positive breast cancer. Estrone (E 1 ) was the predominant estrogen in premenopausal breast adipose tissue, and E 1 and mRNA expression of CYP19A1 in adipose tissue correlated positively with BMI. Adipose tissue estradiol (E 2 ) concentrations fluctuated during the menstrual cycle, similarly to the serum concentrations. In women with breast cancer median adipose tissue E 1 (1519 vs. 3244, p < .05) and E 2 (404 vs. 889 pmol/kg, p < .05) levels were lower in the follicular than in the luteal phase whereas in control women no significant differences were observed. In the follicular phase, mRNA expressions of HSD17B1 (median 0.06; interquartile range 0.05-0.07 vs. 0.17; 0.03-0.2, p = .010) and CYP19A1 (0.08; 0.07-0.14 vs. 0.22; 0.09-0.54, p = .025) were lower in women with breast cancer than in controls. In conclusion, the changes in adipose tissue E 1 and E 2 concentrations and the estrogen-regulating CYP19A1 and HSD17B1 during the menstrual cycle may be related to dysfunctional local estrogen metabolism in women with breast cancer.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontinue postmenopausal hormone therapy (HT)., Methods: We analyzed the risk of death due to cardiac (n = 5,204) and cerebrovascular (n = 3,434) causes in Finnish women who discontinued systemic HT during 1994 to 2013 (n = 432,775). The risks were compared with those in the age-matched female background population and with those in age-matched HT users. Women diagnosed with cardiac or cerebrovascular events within 1 year before discontinuation of HT were excluded (n = 8,711)., Results: Women younger than 60 years at discontinuation of HT showed a significantly increased risk of cardiac death (after ≤5 y of HT exposure, standardized mortality ratio [SMR] 1.52, 95% CI 1.13-2.00; after >5 y of exposure, SMR 2.08, 95% CI 1.44-2.90) and stroke death (after ≤5 y of exposure, SMR 2.62, 95% CI 2.07-3.28; after >5 y of exposure, SMR 3.22, 95% CI 2.29-4.40) during the first year after treatment as compared with age-matched female background population. When compared with HT users, elevations in risks of cardiac and stroke deaths were even higher. Increased mortality risks were limited to the first post-HT year because increases in risks vanished or markedly decreased when the follow-up time was extended over more than 1 year., Conclusions: Discontinuation of postmenopausal HT may be associated with increased risk of cardiac and stroke death in the first posttreatment year. Further investigation is required to evaluate causality of the observed associations.

Context: In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots., Objective: We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women., Design, Setting, Patients, and Interventions: AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction., Results: Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005)., Conclusions: Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women., (Copyright © 2017 Endocrine Society)

Objective: The aim of the study was to compare the effects of different hormone therapies on cardiac repolarization in recently postmenopausal women with and without hot flashes., Methods: We recruited 150 healthy women: 72 with and 78 without hot flashes. They were randomized and treated for 6 months with transdermal estradiol (1 mg/day), oral estradiol (OE) alone (2 mg/day) or combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo. Cardiac repolarization was assessed by measuring QT intervals, rate-dependence of QT-end interval, and T waves from 24-hour electrocardiographic recording before and during hormone therapy, comprising a total of over 20 million QT-interval measurements., Results: Hot flashes were accompanied with shortened median T-peak - T-end interval (at RR interval of 700, 800, and 900 ms; P = 0.040, 0.020, and 0.032; η = 0.35, 0.39, and 0.37; respectively) during the use of OE but not transdermal estradiol. In contrast, the addition of MPA to OE lengthened the maximal QT-end (at RR interval of 500 ms, P = 0.016, η = 0.27) and the maximal T-peak - T-end interval (at RR interval of 500 and 600 ms; P = 0.016 and 0.032; η = 0.25 and 0.22, respectively). These effects were not seen in women without hot flashes., Conclusions: Hot flashes predict beneficial shortening in cardiac repolarization during OE, but not if MPA is combined with OE. These data may provide one explanation for MPA-related cardiac hazards in epidemiological studies.

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) 22-36kg/m 2 ] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/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=5.9kg/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 17β-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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Reduction in the number of gynecological operations has made resident training more difficult in gynecological surgery. We used electronic educational material to supplement traditional apprentice model in resident surgical education. Our aim was to evaluate effectiveness of a web-based course in knowledge gaining among residents with various levels of clinical experience., Design: In prospective interventional study, the level of knowledge was assessed before and after taking the course., Setting: All Finnish residents in obstetrics and gynecology were invited to participate., Participants: Fifty-eight voluntary residents from all 5 University districts were allocated in 3 groups according to the experience., Results: Fifty-eight residents replied to the precourse questionnaire, and 33 (57%) of them filled in the postcourse questionnaire. Significant knowledge gain was detected in each experience group. In the less experienced group, the mean score (max: 110) increased from 81.9 to 89.3 (p = 0.009), in the middle group from 90.4 to 97.9 (p = 0.003), and in the most experienced group from 94.8 to 100.0 (p = 0.017). The participants rated the usefulness of the course as 4.8 in the Likert scale 1 to 5, and all intended to return to the course., Conclusions: We found a significant increase in scores in every level of clinical experience. Thus, the course could be used as an educational tool., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Context: There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dementia (VD) and Alzheimer's disease (AD)., Objective: We analyzed the mortality risk attributable to VD or AD in women with a history of HT use., Design, Patients, Interventions, and Main Outcome Measures: Finnish women (n = 489,105) using systemic HT in 1994 to 2009 were identified from the nationwide drug reimbursement register. Of these women, 581 died of VD and 1057 of AD from 1998 to 2009. Observed deaths in HT users with <5 or ≥5 years of exposure were compared with deaths that occurred in the age-standardized female population. Furthermore, we compared the VD or AD death risk of women who had started HT at <60 vs ≥60 years of age., Results: Risk of death from VD was reduced by 37% to 39% (<5 or ≥5 years of exposure) with the use of any systemic HT, and this reduction was not associated with the duration or type (estradiol only or estradiol-progestin combination) of HT. Risk of death from AD was not reduced with systemic HT use <5 years, but was slightly reduced (15%) if HT exposure exceeded 5 years. Age at systemic HT initiation (<60 vs ≥60 years) did not affect the death risk reductions., Conclusion: Estradiol-based HT use is associated with a reduced risk of death from both VD and AD, but the risk reduction is larger and appears sooner in VD than AD., (Copyright © 2017 by the Endocrine Society)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The role of postmenopausal hormone therapy (HT) in the incidence of acute coronary syndrome (ACS) has been studied extensively, but less is known of the impact of HT on the mortality risk due to an ACS., Study Design and Main Outcome Measures: We extracted from a population-based ACS register, FINAMI, 7258 postmenopausal women with the first ACS. These data were combined with HT use data from the National Drug Reimbursement Register; 625 patients (9%) had used various HT regimens. The death risks due to ACS before admission to hospital, 2-28, or 29-365days after the incident ACS were compared between HT users and non-users with logistic regression analyses., Results: In all follow-up time points, the ACS death risks in HT ever-users were smaller compared to non-users. Of women with HT ever use, 42% died within one year as compared with 52% of non-users (OR 0.62, p<0.001). Most deaths (84%) occurred within 28days after the ACS, and in this group 36% of women with ever use of HT (OR 0.73, p=0.002) and 30% of women with ≥5year HT use (OR 0.54, p<0.001) died as compared to 43% of the non-users. Age ≤60 or >60 years at the HT initiation was accompanied with similar reductions in ACS mortality risk., Conclusions: Postmenopausal HT use is accompanied with reduced mortality risk after primary ACS., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mortality. We analyzed nationwide Finnish data on breast cancer mortality risk in women using HT consisting of estradiol-only therapy (ET) or estrogen-progestogen therapy (EPT)., Methods: In total, 489,105 women using HT in 1994 to 2009, traced from the nationwide reimbursement register, were followed from the HT initiation (3.3 million cumulative exposure years) to breast cancer death (n = 1,578 women). The observed deaths were compared with those in the age-standardized background population., Results: The breast cancer mortality risk was reduced in all HT users with exposure for at most 5 years (standardized mortality ratio 0.56; CI 0.52-0.60), more than 5 to 10 years (0.46; 0.41-0.51), or more than 10 years (0.62; 0.56-0.68). A significantly larger risk reduction was detected in the 50 to 59 years age group (0.33; 0.29-0.37) compared with 60 to 69 (0.64; 0.59-0.70) or 70 to 79 (0.78; 0.69-0.87) years age groups. The death risk reductions in ET users tended to be larger in all age groups compared with EPT users, with a significant difference only in the 70 to 79 years age group (0.66; 0.57-0.76 vs 0.88; 0.77-1.00). The age at HT initiation, regardless whether ET or EPT, showed no association with breast cancer mortality., Conclusions: In the Finnish unselected population, breast cancer is fatal in 1 of 10 patients. Our data imply that this risk is prevalent in 1 of 20 patients with history of HT use. This is an important message for women considering or already using HT.

Introduction and Hypothesis: The objective was to assess safety and clinical outcomes in women operated on using the Uphold™ Lite Vaginal Support System., Methods: We carried out a 1-year, multicenter, prospective, single cohort study of 207 women with symptomatic Pelvic Organ Prolapse Quantification (POP-Q) stage ≥2 apical pelvic organ prolapse, with or without concomitant anterior vaginal wall prolapse. Safety data were collected using a standardized questionnaire. Anatomical outcome was assessed by the POP-Q and subjective outcomes by the Pelvic Floor Distress Inventory after 2 months and 1 year using a one-way repeated measures analysis of variance. Pain was evaluated using a visual analog scale., Results: The overall rate of serious complications was 4.3 % (9 out of 207 patients), including 3 patients with bladder perforations, 1 with bleeding >1,000 ml, 2 who had undergone re-operations with complete mesh removal because of pain, and 3 surgical interventions during follow-up because of mesh exposure. POP-Q stage ≤1 after 1 year was 94 % and subjective symptom relief was reported by 91 % of patients (p < 0.001). Pain after 2 months and 1 year was 60 % lower compared with the preoperative mean (p < 0.001). Minor complications occurred in 20 women (9.7 %) and were dominated by lower urinary tract dysfunction. No predisposing risk factors for complications were found., Conclusions: The Uphold™ Lite procedure in women with apical pelvic organ prolapse provided satisfactory restoration of vaginal topography and symptom relief. However, serious complication rates were largely comparable with those of other transvaginal mesh kits.

Context: The "window of opportunity hypothesis" refers to data indicating that conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, if initiated before 60 years of age, protects the heart but endangers it if initiated later (Women's Health Initiative study). Less is known about the "window of opportunity hypothesis" with natural estradiol alone (ET) or with various progestins in combination with estradiol (EPT)., Objective: We related the death risk from coronary heart disease (CHD) in users of ET or EPT to the age at the initiation of therapy and to the progestin component of EPT. Design, Patients, Interventions, and Main Outcome Measures: Altogether, 498 105 women had used ET or EPT containing medroxyprogesterone acetate, norethisterone acetate, dydrogesterone, other progestins, or tibolone during 3.7 million person-years during 1994-2009. Women were followed from the therapy initiation to death, or to the end of year 2009. The risk of CHD death in hormone users was compared with that in the age-matched background population using standardized mortality ratio with 95% confidence intervals., Results: Age younger than 60 rather than older than 60 years at the initiation of ET (standardized mortality ratio, 0.53; 95% confidence interval, 0.47-0.59 vs 0.76; 0.71-0.82), EPT with norethisterone acetate (0.45; 0.41-0.49 vs 0.74; 0.67-0.81), or tibolone (0.35; 0.26-0.47 vs 1.01; 0.67-1.46) therapy lasting for less than 5 years was associated with significantly greater decreases in the CHD death risk. A similar tendency was also seen for other EPT groups and for longer use. In all hormone users, the CHD death risk was smaller the earlier the use of ET or EPT had started (P < .05); this phenomenon was unrelated to the progestin component of EPT., Conclusions: Estradiol-based hormone therapies are accompanied with larger CHD mortality risk reductions the earlier the therapies are initiated. The progestin component of EPT does not modify this "timing effect."

Objective: Menopausal hot flushes are associated with elevated activity of the sympathetic nervous system and may be related to increased risk for cardiovascular events. Sympathetic activation may trigger severe arrhythmias by modulating cardiac repolarization. The aim of this study was to evaluate the impact of hot flushes on cardiac repolarization in postmenopausal women with and without hot flushes., Methods: We assessed 150 recently postmenopausal healthy women-72 with hot flushes and 78 without hot flushes. They underwent 24-hour electrocardiographic recording, comprising a total of over 10,000,000 QT-interval measurements. The cardiac repolarization was assessed by measuring QT-intervals, heat rate dependence of QT-end intervals, and T-waves., Results: The maximal QT-end interval was shorter in women with hot flushes compared with those without hot flushes (481 ± 64 ms vs 493 ± 50 ms; P = 0.046). There were no differences between the rate dependence of QT-end intervals and T-wave measures between the groups. During the night-time hot flush period, we detected a steeper rate-dependence of QT-end intervals and a longer maximal T-peak-T-end interval (117 ± 54 ms vs 111 ± 56 ms; P < 0.001) compared with the control period., Conclusions: Women with hot flushes did not have clinically significant differences in ambulatory cardiac repolarization measurements compared with asymptomatic women. However, a sudden sympathetic surge occurring during the night-time hot flush may have direct effects on cardiac repolarization.

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., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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 17β-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., (© 2016 European Society of Endocrinology.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)