| 1. |
- Alesi, Simon, et al.
(författare)
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Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
- 2023
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Ingår i: EClinicalMedicine. - 2589-5370. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS.We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640.From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n=961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens+lifestyle were superior to metformin+lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]:-1.59 [-3.06,-0.12], p=0.03; I2=74%), SHBG (7.70nmol/l [0.75, 14.66], p=0.03; I2=0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97,-0.26], p=0.03; I2=0% and-1.12 [-1.44,-0.79], p<0.0001, I2=0%, respectively), but were not superior to placebo+lifestyle for hirsutism (-0.93, [-3.37, 1.51], p=0.45; I2=76%) or SHBG (9.72nmol/l [-0.71, 20.14], p=0.07; I2=31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58,-2.39], p<0.0001, I2=1%), and resulted in lower androstenedione levels (-0.30ng/ml [-0.50,-0.10], p=0.004; I2=0%). Combination treatment with anti-androgens+metformin+lifestyle resulted in lower testosterone compared with metformin+lifestyle (-0.29nmol/l [-0.52,-0.06], p=0.01; I2=61%), but there were no differences in hirsutism when anti-androgens+metformin+lifestyle were compared with either anti-androgens+lifestyle or metformin+lifestyle. In limited meta-analyses (n=2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP±placebo, with no differences in other outcomes.Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics.National Health and Medical Research Council (NHMRC) of Australia Monash University.
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| 2. |
- Forslund, Helena, 1978-, et al.
(författare)
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Grazing and geographic range of the Baltic seaweed Fucus radicans (Phaeophyceae)
- 2012
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Ingår i: Marine Biology Research. - : Informa UK Limited. - 1745-1000 .- 1745-1019. ; 8:4, s. 322-330
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Tidskriftsartikel (refereegranskat)abstract
- The range of the recently described seaweed Fucus radicans is limited to the Bothnian Sea and the northern Baltic Sea while the range of the sympatric Fucus vesiculosus extends outside the Baltic Sea. Here we present results from a survey of the distribution and relative abundance of F. radicans and F. vesiculosus and abundance of associated herbivores along the range of F. radicans in Sweden. Both Fucus species were equally common. Herbivores were found in significantly higher numbers on F. radicans. The range of the herbivore Idotea balthica overlaps the southern range of F. radicans and is known to decrease the abundance of fucoids through grazing. We therefore hypothesized that if I. balthica has a preference for F. radicans it could affect the range of F. radicans. To test the preference of I. balthica we performed a bioassay where it had a choice between F. radicans and F. vesiculosus. Another bioassay was performed with the most common herbivore in our survey, Gammarus spp. Both herbivores consumed significantly more F. radicans than F. vesiculosus. Our results indicate that grazing may be an important factor in limiting the southern range of F. radicans along the Swedish coast.
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| 3. |
- Forslund, Helena, 1978-
(författare)
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Grazing and the geographical range of seaweeds : The introduced Fucus evanescens and the newly described Fucus radicans
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Along the coast of temperate oceans brown algae of the genus Fucus form dense stands on rocky shores and are keystone species of the coastal ecosystem. These large seaweeds are perennial and function as substrate for many sessile marine organisms, provide shelter for fauna and juvenile fish, and are food source. A number of abiotic (e.g. wave-exposure, salinity and substrate) and biotic (e.g. herbivory and competition) factors structures these communities and determines the abundance and composition of fucoids at each specific site. Earlier studies have shown that herbivores may reduce growth of fucoids, thus affecting their distribution, and at high densities eliminate the species from previously occupied sites. In my thesis I focused on investigating herbivore-seaweed interactions and whether such interactions could influence the geographical range limits of Fucus species. A set of laboratory bioassays and a field survey were conducted (1) to investigate the resistance to grazing by a generalist gastropod between introduced (to Sweden) and native (Iceland) Fucus evanescens (Paper I), (2) to study the distribution pattern of F. radicans and F. vesiculosus along the Swedish coast and specifically the southern limit of F. radicans, (3) to examine the abundance of herbivores in these two species, and (4) to test the hypothesis that Idotea baltica may contribute to restrict F. radicans to the Bothnian Sea (objective 2-4; Paper II). Fucus evanescens, a species that was introduced to the Swedish coast about 100 years ago, was found to be more resistant to grazing by L. littorea compared to F. evanescens from the native Icelandic populations. It was also shown to contain a higher amount of phlorotannins; a putative chemical defence to herbivory. This indicates that development of resistance to herbivory could be important for a successful introduction and survival in a new range. No gradual change in the proportion, measured as % cover of either F. radicans or F. vesiculosus was found inside the range of F. radicans and its southernmost limit was abrupt without any corresponding abrupt change in any abiotic factor, e.g. salinity. Herbivores, i.e. Idotea spp., Gammarus spp. and Theodoxus fluviatils were found to be more abundant in F. radicans than in F. vesiculosus thalli indicating a habitat preference for F. radicans. Further, Idotea baltica, whose range only overlaps with that of F. radicans in the south, was shown to prefer F. radicans over F. vesiculosus, possibly due to its lower content of phlorotannins. Based on these findings I propose that Idotea species may contribute in restricting the southern range of F. radicans, although further experiments, especially regarding competition with the larger F. vesiculosus need to be performed. In conclusion, biotic interactions e.g. the ability of to resist herbivore grazing by e.g. high phlorotannin content or having a structure less attractive as habitat to herbivores may be of importance in determining the geographic range of fucoids.
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| 4. |
- Forslund, Helena, 1978-
(författare)
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Herbivory, phenotypic variation, and reproductive barriers in fucoids
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Along the shores of the Northern hemisphere Fucus (Phaeophyceae) species are a prominent presence, providing substrate, shelter, and food for many species. Fucus evanescens, a non-indigenous species (NIS) in Sweden, and F. radicans, a recently described species that so far has only been found inside the species poor Baltic Sea, are the focus of this thesis.Interactions with enemies (e.g. predators, herbivores, parasites) have been shown to play a role in the success of NIS. The low consumption of Fucus evanescens by the generalist gastropod Littorina littorea in Sweden was found to depend on high levels of chemical defense in the introduced population, not the failure of the herbivore to recognize F. evanescens as suitable food.A survey of the relative abundance of F. radicans and F. vesiculosus and the most common associated fauna along the Swedish Bothnian Sea coast showed that F. radicans and F. vesiculosus are equally abundant throughout the range of F. radicans. The most common associated fauna were found to be more abundant on F. radicans compared to F. vesiculosus. In Sweden, where F. radicans had lower levels of defense chemicals than F. vesiculosus, F. radicans was grazed more than F. vesiculosus in bioassays. This could, together with other factors, influence the range of F. radicans.Fucus radicans and F. vesiculosus are closely related, recently separated, and growing sympatrically, therefore, possible reproductive barriers between F. radicans and F. vesiculosus were studied. In Estonia F. radicans and F. vesiculosus reproduces at different times of the year. No such clear reproductive barrier was found between the two species in Sweden where they reproduce at the same time and fertilization success and germling survival were the same for hybrids as for F. vesiculosus.Since the high clonality of F. radicans means that the gentic diversity in F. radicans populations is low I investigated how genetic diversity translates to phenotypic diversity in nine traits. Phlorotannin levels, recovery after desiccation, and recovery after freezing showed inherited variation, while the other six traits showed no variation related to genetic diversity. Phenotypic variation in populations of F. radicans will be higher in populations with higher genetic diversity and this might be beneficial to the community.
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| 5. |
- Forslund, Helena, 1978-, et al.
(författare)
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Higher resistance to herbivory in introduced compared to native populations of a seaweed
- 2010
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Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 164:3, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Non-indigenous species (NIS) are important components of global change, and in order to manage such species it is important to understand which factors affect their success. Interactions with enemies in the new range have been shown to be important for the outcome of introductions, but thus far most studies on NIS-enemy interactions have considered only specialist herbivores in terrestrial systems. Here we present the results from the first biogeographic study that compares herbivore resistance between populations in the native and new region of a non-indigenous seaweed. We show that low consumption of the non-indigenous seaweed by a generalist herbivore is caused by higher chemical defence levels and herbivore resistance in the new range-and not by the failure of the herbivore to recognise the non-indigenous seaweed as a suitable host. Since most seaweed-herbivore interactions are dominated by generalist herbivores, this pattern could be common in marine communities. Our results also reveal that traits used to predict the invasive potential of species, such as their resistance to enemies, can change during the invasion process, but not always in the way predicted by dominant theories.
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| 6. |
- Forslund, Helena, 1978-, et al.
(författare)
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Reproduction and reproductive isolation in Fucus radicans (Phaeophyceae)
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Ingår i: Marine Biology Research. - 1745-1000 .- 1745-1019.
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Tidskriftsartikel (refereegranskat)abstract
- Recent morphological and genetic studies show that Fucus radicans is a separate species from the sympatric F. vesiculosus. Fucus radicans recently diverged from F. vesiculosus in the Baltic Sea where populations grow in mixed stands. Thus, strong reproductive barriers are expected to be in place to prevent introgression. The seasonal timing of reproduction of the two species in Estonia was shown to be different, likely forming an effective pre-zygotic reproductive barrier. In Sweden, however, no such temporal difference was found. We artificially crossed Swedish F. radicans and F. vesiculosus to identify other potential reproductive barriers. Fertilization success and survival was equally high within and between species in the artificial crossings, suggesting no early post-zygote barriers. Both species recruit new thalli both sexually and asexually, but F. radicans is generally more asexual than F. vesiculosus. By studying their reproductive efforts we found that Swedish F. radicans allocates more resources to adventitious branches than to gamete production compared to F. radicans in Estonia and F. vesiculosus in both Sweden and Estonia. This indicates that Swedish F. radicans has an asexual reproductive strategy while Estonian F. radicans and F. vesiculosus have sexual reproductive strategies.
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| 7. |
- Forslund, Maria, 1978, et al.
(författare)
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Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis.
- 2023
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Ingår i: European journal of endocrinology. - 1479-683X. ; 189:1
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Tidskriftsartikel (refereegranskat)abstract
- To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).A systematic review and meta-analysis was performed, Prospero CRD42022345640.MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.
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| 8. |
- Forslund, Maria, 1978, et al.
(författare)
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International evidence-based guideline on assessment and management of PCOS-A Nordic perspective.
- 2024
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - 1600-0412. ; 103:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence-based guideline on assessment and management of PCOS was published, and an updated extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti-Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long-term follow-up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.
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| 9. |
- Johannesson, Kerstin, 1955, et al.
(författare)
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Phenotypic variation in sexually and asexually recruited individuals of the Baltic Sea endemic macroalga Fucus radicans : in the field and after growth in a common-garden
- 2012
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Ingår i: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 12, s. 2-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most species of brown macroalgae recruit exclusively sexually. However, Fucus radicans, a dominant species in the northern Baltic Sea, recruits new attached thalli both sexually and asexually. The level of asexual recruitment varies among populations from complete sexual recruitment to almost (> 90%) monoclonal populations. If phenotypic traits have substantial inherited variation, low levels of sexual activity will decrease population variation in these traits, which may affect function and resilience of the species. We assessed the level of inherited variation in nine phenotypic traits by comparing variation within and among three monoclonal groups and one group of unique multilocus genotypes (MLGs) sampled in the wild.RESULTS: Of the nine phenotypic traits, recovery after freezing, recovery after desiccation, and phlorotannin content showed substantial inherited variation, that is, phenotypic variation in these traits were to a large extend genetically determined. In contrast, variation in six other phenotypic traits (growth rate, palatability to isopod grazers, thallus width, distance between dichotomies, water content after desiccation and photochemical yield under ambient conditions) did not show significant signals of genetic variation at the power of analyses used in the study. Averaged over all nine traits, phenotypic variation within monoclonal groups was only 68% of the variation within the group of different MLGs showing that genotype diversity does affect the overall level of phenotypic variation in this species.CONCLUSIONS: Our result indicates that, in general, phenotypic diversity in populations of Fucus radicans increases with increased multilocus genotype (MLG) diversity, but effects are specific for individual traits. In the light of Fucus radicans being a foundation species of the northern Baltic Sea, we propose that increased MLG diversity (leading to increased trait variation) will promote ecosystem function and resilience in areas where F. radicans is common, but this suggestion needs experimental support.
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| 10. |
- Melin, Johanna, et al.
(författare)
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Metformin and combined oral contraceptive pills in the management of polycystic ovary syndrome: a systematic review and meta-analysis.
- 2024
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Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 109:2
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is affecting more than every tenth woman.As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin and combination treatment were evaluated.Ovid Medline, Embase, PsycINFO, All EBM and CINAHL were searched.Women with PCOS included in randomized controlled trials (RCT).We calculated mean differences (MD) and 95% confidence intervals (CI) regarding anthropometrics, metabolic and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE was performed.The search identified 1660 publications, 36 RCTs were included. For hirsutism no differences were seen when comparing metformin versus COCP, nor when comparing COCP versus combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08, 95% CI 4.81; 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/l, 95% CI -174.46; -62.75) and testosterone (0.48 nmol/l,95% CI 0.32; 0.64) compared with COCP. COCP was inferior for FAI (0.58, 95% CI 0.36; 0.80) and SHBG (-16.61 nmol/L, 95% CI -28.51; -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/l, 95%CI -40.65; -13.59) and triglycerides (-0.15 mmol/l, 95%CI -0.29; -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/l, 95%CI 7.79; 26.26) and insulin resistance (0.44, 95%CI 0.17; 0.70) compared with combination treatment.The choice of metformin or COCP treatment should be based on symptoms, noting that there are some biochemical benefits from combination treatment, targeting both major endocrine disturbances seen in PCOS; hyperinsulinemia and hyperandrogenism.
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