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IntroductionDysmenorrhea and heavy menstrual bleeding are the most common symptoms in adenomyosis, in addition to infertility and chronic pelvic pain. Hysterectomy is a common treatment for adenomyosis symptoms with curative effect on heavy menstrual bleeding but with less studied effects on pain reduction.Material and methodsThis is a nationwide retrospective register-based cohort study including all hysterectomized patients with pathology-verified adenomyosis between 1 January 2012 and 31 December 2015 with a long-term follow-up three years pre- and three years postoperatively. Two national registers were linked in order to describe the primary outcome of proportion with use of opioids among hysterectomized patients with and without adenomyosis pre- and postoperatively. Logistic and multinomial regression models were used.ResultsA total of 2,228 (15%) patients had pathology-verified adenomyosis. Overall opioid use was 18.6% and 21.1% three years before and three years after surgery, respectively. Results showed a significantly increased risk of opioid use three years after hysterectomy in patients with preoperative use of opioids and antidepressants (adjusted Odds Ratio (aOR) 5.7, 95% Confidence Interval (CI) 4.5-7.2 and aOR 1.4, 95% CI 1.1-1.8). The risk of needing long-term opioids was higher among patients with smaller uteri (ConclusionsHysterectomy does not reduce opioid use among adenomyosis patients in long-term follow-up, although the subjective reduction of pain was not investigated in this study. Women with preoperative use of opioids/antidepressants and uterine size

Background Previous investigations of time-to-pregnancy recognition have analysed data from national surveys and clinics, but this has not been investigated in the context of digital fertility applications. Timely pregnancy recognition can help individuals in health and pregnancy management, reducing maternal and foetal risk and costs, whilst increasing treatment options, availability, and cost.Methods This dataset contained 23,728 pregnancies (conceived between June 2018 and December 2022) from 20,429 participants using a Food and Drug Administration (FDA) cleared fertility app in the United States. Most participants (with non-missing information) identified as Non-Hispanic White, and one-third reported obtaining a university degree. We used two-tailed Welch’s t-test, Mann–Whitney U-test, and two-tailed Z-tests to compare time to pregnancy recognition between those using the app to conceive or contracept.Results Participants using an app to conceive recognised pregnancy on average at 31.3 days from last menstrual period (LMP) compared to 35.9 days among those using the app to prevent pregnancy.Conclusion Generalisability is limited, as all participants were using a fertility app and had relatively homogenous sociodemographic characteristics.

Abstract Background It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). Methods This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. Results Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. Conclusions Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. Trial registration details Not applicable.

Abstract Background The National Institute for Health and Care Excellence advises that considerations around quality of life should be made when assessing and treating heavy menstrual bleeding. A quick and reliable method for women to assess the impact of HMB on their quality of life might encourage help-seeking. This research aimed to develop a new 10-item measure of menstrual quality of life (the PERIOD-QOL). Methods Three pilot studies describe PERIOD-QOL development and a cross-sectional survey (N = 376) assessed PERIOD-QOL scores in women who reported HMB and those who did not. A population sample of women (mean age 30.29, SD = 9.06) completed the PERIOD-QOL and rated their menstrual bleeding as heavy/very heavy/extremely heavy (HMB group) or very light/light/moderate bleeding (LMMB) group. Data were analysed using independent samples Analysis of Variance and independent samples t-tests. Results Cronbach’s Alpha for the PERIOD-QOL = .88. A significant reduction in PERIOD-QOL scores was found across the 6 levels of bleeding from very light to extremely heavy, and significantly lower PERIOD-QOL scores were reported in the HMB than the LMMB group. Conclusion The results suggest that the PERIOD-QOL is a reliable measure and that women experiencing HMB reported significantly lower menstrual quality of life than those who did not. Further validation of the PERIOD-QOL is required to determine its relationships with existing measures of menstrual quality of life and to establish whether PERIOD-QOL scores are associated with decisions to seek help from health professionals and with verified diagnoses of conditions that cause HMB.

Objective To evaluate the efficacy, feasibility and acceptability of microwave ablation (MWA) compared to uterine artery embolization (UAE) as treatment for uterine fibroids. Method A randomized controlled superiority trial, including premenopausal women 30–55 years, with symptomatic uterine fibroids without any single fibroid exceeding mean diameter of eight centimeters. Patients were randomized to receive microwave ablation, performed abdominally or vaginally, or to uterine artery embolization. The primary outcome was volume difference of the three largest fibroids at 6 months post treatment evaluated by magnetic resonance imaging (MRI) by a blinded radiologist analyzed by Mann–Whitney U-test. Secondary outcomes included symptom severity score (SSS), health related quality of life (HR-QoL), amount of menstrual bleeding, postoperative pain, length of hospitalization, need for additional treatment, adverse events and if patients would recommend the treatment to a friend. Results Patients were recruited from 30 January 2017 to 12 September 2019, with a total of 17 patients treated in each group from May 2017 to December 2019. Superiority of MWA could not be established. The volume reduction was 41.8% (Interquartile range, IQR, 14–63) in the MWA group compared to 62.2% (IQR 34.9–80.1) in the UAE group (p = 0.29). Effects on symptoms, HR-QoL and acceptability did not differ between groups. Days of hospitalization and sick leave were significantly fewer in the MWA group (p

Objective To study long-term effects in patients treated with microwave ablation (MWA) for symptomatic uterine fibroids and investigate fibroid characteristics predictive of successful treatment.Method Women who received MWA treatment for uterine fibroids in a previous study were included. A total of 16 patients underwent contrast enhanced MRI before treatment, postoperatively at 6 months and at long-term follow-up, to assess volumes of treated fibroids (n = 42). Long-term MRI was performed between 16 and 36 months after treatment [median 22 months, interquartile range (IQR) 18.5–27]. Validated questionnaires for evaluation of uterine fibroid symptoms and menstrual bleeding (UFS-QoL and PBAC) were used to assess long-term effects on symptoms. The degree of shrinkage was correlated to vascularization and T2 signal intensity (SI) at preoperative MRI and location of fibroids according to the FIGO classification, using the Mann–Whitney U test.Results Most patients (82%) reported improvement up to 3 years after treatment. Out of 42 treated fibroids, 35 (83%) continued to shrink over time with median relative volume reduction of 77% (IQR 39–95). For eight fibroids (19%) which showed low vascularization on the pretreatment MRI, there was less shrinkage compared to well-vascularized fibroids (p = 0.01). Most fibroids (79%) showed iso- to hyperintense T2 signal on preoperative MRI and showed a higher grade of shrinkage than hypointense fibroids (p = 0.02).Conclusion After microwave treatment improvement is maintained for most patients up to 36 months and most fibroids showed continuous shrinkage. Preoperative vascularization, high T2 SI and submucosal location predicted continuous volume reduction. However, to confirm this, larger studies are needed.

Abstract This study aimed to assess the association between interpregnancy interval (IPI)—the time from childbirth to conception of the next pregnancy—and maternal and neonatal morbidity. The World Health Organization (WHO) currently recommends an IPI of at least 24 months after a live birth to reduce adverse birth outcomes. However, assessing the relationship between IPI and perinatal outcome is complicated by confounding factors. We conducted a nationwide population-based cohort study using Swedish registry data, allowing for adjustment of maternal characteristics and health at first birth. The study population consisted of all women with a singleton, live, and vaginal first birth with a second singleton birth within five years during 1997–2017, covering 327,912 women and 655,824 neonates. IPI was grouped into six-month intervals with 24–29 months as the reference. The association between IPI and morbidity was examined using multivariate logistic regression. For women having a vaginal delivery at their first birth, intervals 24–29 months were associated with increased maternal and neonatal morbidity. Our findings question the relevance of WHO’s recommendation of an IPI of at least 24 months in a high-income country.

Abstract Background Although previous studies report an association between Premenstrual Dysphoric Disorder (PMDD) and suicidal ideation, most studies have only established a provisional and retrospective diagnosis of PMDD fundamentally invalidating the diagnosis. Therefore, the aim of this study was to describe the prevalence and to explore correlates of current suicidal ideation in the late luteal phase in women with prospectively assessed and confirmed PMDD. Methods Participants were 110 women who attended the pre-randomization baseline visit of two randomized placebo-controlled clinical trials between January 15, 2017 and October 19, 2019. PMDD was diagnosed prospectively in line with DSM-5 criteria. Current suicidal ideation was measured by the MADRS-S in the late luteal phase. Descriptive statistics were presented and logistic regression analyses were carried out to explore the association between psychosocial and health characteristics and current suicidal ideation, presenting unadjusted odds ratios (OR) and 95% confidence intervals (CI). Results Current suicidal ideation was reported by nearly 40% of women with confirmed PMDD (n = 43, 39.1%). Previous psychological treatment for PMDD and higher depressive symptoms in the late luteal phase were positively associated with current suicidal ideation (OR 5.63, 95% CI 1.07–29.49, and OR 1.17, 95% CI 1.10–1.25, respectively), whereas higher ratings of self-rated health were associated with lower odds ratios for current suicidal ideation (OR 0.98, 95% CI 0.96–0.99). Conclusions A substantial proportion of women with confirmed PMDD report current suicidal ideation in the late luteal phase. Results point to a need for better awareness and screening of suicidal ideation in women with PMDD.

Summary: Background: Evidence on a possible association between newer hormonal contraceptives (HC) and risk of breast cancer remains inconclusive, especially as concerns progestogen-only methods. Methods: In this nationwide prospective cohort study, all Swedish women aged 15–34 at study start on January 1st 2005, or who turned 15 years during the study period, were followed until December 31st 2017. Using information from seven National Registers, we assessed the risk ratio of developing breast cancer and breast cancer in situ in relation to different HC using Poisson regression. We adjusted the analyses for several known confounders of breast cancer. Findings: This cohort included 1.5 million women providing more than 14 million person-years. During the study period, 3842 women were diagnosed with breast cancer. Compared with never users of any HC, we found no increased risk of developing breast cancer among current users of any combined HC, IRR 1.03 (0.91–1.16), whereas current users of progestogen-only methods had an increased risk of developing breast cancer, IRR 1.32 (1.20–1.45). Across all types of HC, the risk of developing breast cancer appeared to be highest the first five years of use (combined HC IRR 1.39 (1.14–1.69); progestogen-only methods IRR 1.74 (1.44–2.10). The risk disappeared ten years after the women stopped using HC. The absolute risk of breast cancer per 100,000 women-years was 22.4 for never users, 10.9 for current users of combined HC, and 29.8 for current users of progestogen-only methods. Interpretation: Current use of progestogen-only methods is associated with a small increased risk of developing breast cancer, whereas we could only detect an increased risk among users of combined HC during the first five years of use. This may partly be explained by a selective prescription of progestogen-only methods to women with risk factors for breast cancer, like smoking or obesity. As the absolute risk of breast cancer was small, the many health benefits associated with HC must also be taken into account in contraceptive counselling. Funding: This study was funded by the Swedish Cancer Society and by the Uppsala County Council, the Faculty of Medicine at Uppsala University.

Introduction Data suggest that micronised progesterone (mP) in menopausal hormone therapy is safer for the breast than synthetic progestins, while protection of the endometrium appears to be less effective. However, comparative randomised trial data are lacking. The objective of the Progesterone Breast Endometrial Safety Study is to investigate breast and endometrial safety of mP versus norethisterone acetate (NETA) in continuous combination with oral oestrogen.Methods and analysis This multicentre trial, conducted at three University Hospitals in Stockholm and Uppsala, Sweden, consists of two phases: part 1 focuses on breast safety and is designed as a double-blind, randomised controlled trial. 260 postmenopausal women will be randomised to 100 mg mP or 0.5 mg NETA per day in continuous combination with 1 mg oestradiol. The primary objective is to compare the treatments with respect to percentage change in mammographic breast density after 12-month treatment. Secondary outcomes are breast proliferation, endometrial histology and proliferation, bleeding pattern, gut and vaginal microbiome, hormone levels and coagulation and metabolic factors, mood, and health-related quality of life. Part 2 features an open, single-arm design to study endometrial safety of 1-year treatment with mP in continuous combination with oestradiol on endometrial pathology (hyperplasia and cancer). We will treat 260 additional women with 100 mg mP/1 mg oestradiol resulting in an endometrial safety population of 390 women. The total number of participants in part 1 and part 2 will be 520.Ethics and dissemination The study protocol was approved by the Swedish Ethical Review Authority (2021-03033) on 29 June 2021 with amendment (2023-01480-02, protocol version 3.1) on 14 March 2023. Results of the study will be published in peer-reviewed journals and presented at scientific meetings.Trial registration number NCT05586724.