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  • 701. Wirtberg, I
    et al.
    Möller, A
    Hogström, L
    Tronstad, S-E
    Lalos, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Life 20 years after unsuccessful infertility treatment2007Inngår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 22, nr 2, s. 598-604Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: This study explores the long-term experience of involuntary childlessness among 14 Swedish women 20 years after their infertility treatment. METHODS: In-depth interviews were conducted. RESULTS: The childlessness had had a strong impact on all the women’s lives and was for all a major life theme. The effects were experienced both on a personal level and on interpersonal and social levels. Half of the women were separated, and in all but one, sexual life was affected in negative and long-lasting ways. The effects of childlessness were especially increased at the time the study was conducted, as the women’s peer group was entering the ‘grandparent phase’. Many coped with their childlessness by caring for others, such as the children of friends or relatives, elderly parents or animals. CONCLUSION: These findings represent a small sample, but they point towards the need for developing models of counselling and support that stimulate self-reflection and strengthen personal resources and empowerment for individuals and couples experiencing involuntary childlessness.

  • 702.
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Reproductive hazards in an industrial setting: an epidemiological assessment1996Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: As more women of childbearing age engage in the workforceand a lot of new chemicals are available, a growing interest of diagnosing andpreventing reproductive disorders due to occupational and environmentalexposure has occurred. The source location of this thesis is the Rönnskärcopper smelter which is situated in the north of Sweden, in the municipality of Skellefteå. Emissions from the smelter, which have diminished during theperiod 1975-1990 include sulphur dioxide and heavy metals, especially lead,arsenic, cadmium, copper, mercury and zinc. Reproductive studies from the1970s in and around the smelter reported increased risks of spontaneousabortions, malformations and lower birth weight. The aim of this thesis wasto perform a broad and long-term epidemiological assessment of adversereproductive outcome in and around the smelter and to determine if theexposed population suffered from reproductive disturbances during the recentdecades.

    Subjects and methods: The study involve two main sources of data. Onewas a retrospective cohort formed through record linkage of populationregisters, the medical birth register (1961-90), the register of congenitalmalformations (1973-90) and the cancer register (1961-90). As another source,information on reproductive history, life-style and work related factors wasobtained from a questionnaire study in 1992. An exposed population wasdefined as smelter workers and their children, and also neighbours to thesmelter and their children.

    Results: In the register study, compared to the reference population, nooverall significant increased risk of malformations, childhood cancer, low birthweight or perinatal death was found in the exposed group. In thequestionnaire study, regarding infertility, no environmental effects were found.Also, no increased risk of a prolonged waiting time to pregnancy or increasedrisk of spontaneous abortions were associated with occupational or environmentalfactors.

    Conclusion: With the lack of a high statistical power in mind, due to smallsample sizes in some of the studies, the summary of our findings includingseveral outcomes, different epidemiological study designs and studies coveringa long period of time gives no evidence for any increased risk of reproductivehazards due to occupational or environmental exposure.

  • 703.
    Wulff, Marianne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Högberg, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Stenlund, Hans
    Occupational and environmental risks of spontaneous abortions around a smelter.2002Inngår i: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 41, nr 2, s. 131-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We found no increase of spontaneous abortion associated to smelter work or to living close to the smelter which could be a result of radically reduced emissions.

  • 704.
    Wulff, Marianne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lalos, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Coitus-dependent and coitus-independent contraceptive methods in women and men2002Inngår i: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 7, nr 2, s. 114-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To study the use of contraceptives in Sweden. Methods: Analysis of the population-based survey 'Sex in Sweden. On the Swedish sexual life 1996'. The survey was analyzed in relation to socio-demographic, lifestyle, sexual and behavioral characteristics as well as attitudes to, and evaluation of, personal experiences. The data included 2810 men and women between 18 and 74 years of age. The results were compared with a similar survey carried out in 1967. Results: During the 30-year period between the 1967 and 1996 surveys, condom use more than halved and use of oral contraceptives increased by 6 percentage points. The decline in the use of condoms did not occur among teenagers but among all other age groups in both men and women. In 1996 the majority (72%) used a reliable contraceptive method, but 29% did not. Coitus-dependent methods were more frequently used by men and women who were below the age of 21, smoked, used alcohol simultaneously with coitus, had casual partners, were more highly educated, were breastfeeding, had coitus less frequently and among those who were most satisfied with their sexual life and their partner relationship. Conclusion: In order to increase the use of more reliable contraceptive methods, three crucial factors should be focused on in counselling and media campaigns: gender, age and the use of coitus-dependent/coitus-independent methods.

  • 705.
    Wulff, Marianne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lalos, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The condom in relation to prevention of sexually transmitted infections and as a contraceptive method in Sweden.2004Inngår i: Eur J Contracept Reprod Health Care, ISSN 1362-5187, Vol. 9, nr 2, s. 69-77Artikkel i tidsskrift (Fagfellevurdert)
  • 706. Yang, Meng
    et al.
    Prescott, Jennifer
    Poole, Elizabeth M.
    Rice, Megan S.
    Kubzansky, Laura D.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    De Vivo, Immaculata
    Tworoger, Shelley S.
    Prediagnosis Leukocyte Telomere Length and Risk of Ovarian Cancer2017Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, nr 3, s. 339-345Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The associations between telomere length and cancer risk are equivocal, and none have examined the association between prediagnosis leukocyte telomere length (LTL) and the risk of developing ovarian cancer. Methods: We prospectively measured LTL collected from 442 ovarian cancer cases and 727 controls in the Nurses' Health Studies and the Northern Sweden Health and Disease Study. Cases were matched to one or two controls on age, menopausal status, and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: LTL was measured a median of 9.5 years before ovarian cancer diagnosis among cases. We observed a decreased risk of ovarian cancer with longer LTL. In multivariable models, women in the top quartile of LTL had an OR for ovarian cancer of 0.67 (95% CI, 0.46-0.97) compared with those in the bottom quartile. Inverse associations were stronger for nonserous cases (ORquartile (4 vs. quartile 1 of LTL) = 0.55, 95% CI, 0.33-0.94) and rapidly fatal cases (i.e., cases who died within 3 years of diagnosis; ORquartile 4 vs. quartile 1 of LTL = 0.55, 95% CI, 0.32-0.95). Conclusions: Our prospective findings suggest that longer circulating LTL may be associated with a lower ovarian cancer risk, especially for nonserous and rapidly fatal cases. The evaluation of LTL in relation to ovarian cancer risk by tumor subtypes is warranted in larger prospective studies. Impact: Prediagnosis LTL may reflect an early event in the ovarian cancer development and could serve as a biomarker to predict future risk.

  • 707. Ylikangas, Stiina
    et al.
    Bäckström, Torbjörn
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Obstetrik och gynekologi.
    Heikkinen, Jorma
    Cost-effectiveness of continuous combined hormone replacement therapy in long-term use: economic evaluation based on a 9-year study in Finland.2007Inngår i: Curr Med Res Opin, ISSN 1473-4877, Vol. 23, nr 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert)
  • 708. Zeleniuch-Jacquotte, A
    et al.
    Shore, R E
    Afanasyeva, Y
    Lukanova, A
    Sieri, S
    Koenig, K L
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Krogh, V
    Liu, M
    Ohlson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Muti, P
    Arslan, A A
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Berrino, F
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Toniolo, P
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer2011Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, nr 9, s. 1458-1464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.

    Methods: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.

    Results: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.

    Conclusion: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

  • 709.
    Åhman, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Edvardsson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Judith Lumley Centre, La Trobe University, Melbourne, Victoria, Australia.
    Fagerli, Tove Anita
    Darj, Elisabeth
    Holmlund, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Small, Rhonda
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Judith Lumley Centre, La Trobe University, Melbourne, Victoria, Australia.
    A much valued tool that also brings ethical dilemmas: a qualitative study of Norwegian midwives' experiences and views on the role of obstetric ultrasound2019Inngår i: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 19, artikkel-id 33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Midwives are the main providers of routine antenatal care services including the routine ultrasound examination in Norway. The ultrasound examination can be perceived by expectant parents not only as a medical examination but also as a social event facilitating attachment to their fetus. This study explores Norwegian midwives' experiences and views on the role of ultrasound in clinical management of pregnancy.

    Methods: A qualitative study design was applied. Twenty-four midwives who all performed obstetric ultrasound examinations were recruited for focus group discussions and individual interviews. Data collection took place in 2015 in five hospitals in two different regions of Norway. Data were analyzed using qualitative content analysis.

    Results: Midwives described obstetric ultrasound examinations as very valuable although doing ultrasounds placed high demands on their operational and counselling skills. Increasing requests for ultrasound from pregnant women were mentioned. Advancements in ultrasound diagnosis were considered to have put the fetus in the position of a patient, and that pregnant women declining ultrasound could be viewed as irresponsible by some health professionals. Ethical concerns were raised regarding the possibility of pregnancy termination when fetal anomalies were detected. Fears were also expressed that prenatal diagnoses including those following ultrasound, might create a society where only perfect' children are valued. However, participants stressed that their intention in performing ultrasound was to optimize pregnancy outcome and thereby assist expectant couples and their unborn children.

    Conclusions: Midwives in Norwegian maternity care services describe obstetric ultrasound as very valuable, playing a central role in pregnancy management by optimizing pregnancy outcomes. Although high demands are placed on operators' technical skills and counseling, midwives described performing obstetric ultrasound as very satisfying work. However, midwives believed that expectant parents' approach to the ultrasound examination, both its medical value and the precious images obtained of the fetus, could put extra strain on the midwives performing ultrasounds. The potential of ultrasound to detect fetal anomalies and the possibility that this may lead to termination of pregnancy, seemed to create some ambivalent feelings in midwives towards its use.

  • 710.
    Åhman, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Edvardsson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Judith Lumley Centre, La Trobe University, Melbourne, Australia.
    Kidanto, Hussein Lesio
    Ngarina, Matilda
    Small, Rhonda
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    'Without ultrasound you can't reach the best decision': midwives' experiences and views of the role of ultrasound in maternity care in Dar Es Salaam, Tanzania2018Inngår i: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 15, s. 28-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To explore Tanzanian midwives' experiences and views of the role of obstetric ultrasound in relation to clinical management of pregnancy, and in situations where maternal and fetal health interests conflict. Method: In 2015, five focus group discussions were conducted with midwives (N = 31) at three public referral hospitals in the Dar es Salaam region as part of the CROss Country Ultrasound Study (CROCUS). Results: Ultrasound was described as decisive for proper management of pregnancy complications. Midwives noted an increasing interest in ultrasound among pregnant women. However, concerns were expressed about the lack of ultrasound equipment and staff capable of skilful operation. Further, counselling regarding medical management was perceived as difficult due to low levels of education among pregnant women. Conclusion: Ultrasound has an important role in management of pregnancy complications. However, lack of equipment and shortage of skilled healthcare professionals seem to hamper use of obstetric ultrasound in this particular low-resource setting. Increased availability of obstetric ultrasound seems warranted, but further investments need to be balanced with advanced clinical skills' training as barriers, including power outages and lack of functioning equipment, are likely to continue to limit the provision of pregnancy ultrasound in this setting.

  • 711.
    Åhman, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Kidanto, Hussein Lesio
    Ngarina, Matilda
    Edvardsson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Judith Lumley Centre, La Trobe University, Melbourne, VIC, Australia.
    Small, Rhonda
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    'Essential but not always available when needed': an interview study of physicians' experiences and views regarding use of obstetric ultrasound in Tanzania2016Inngår i: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 9, artikkel-id 31062Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The value of obstetric ultrasound in high-income countries has been extensively explored but evidence is still lacking regarding the role of obstetric ultrasound in low-income countries.

    Objective: We aimed to explore experiences and views among physicians working in obstetric care in Tanzania, on the role of obstetric ultrasound in relation to clinical management.

    Design: A qualitative study design was applied. Data were collected in 2015, through 16 individual interviews with physicians practicing in obstetric care at hospitals in an urban setting in Tanzania. Data were analyzed using qualitative content analysis.

    Results: Use of obstetric ultrasound in the management of complicated pregnancy was much appreciated by participating physicians, although they expressed considerable concern about the lack of ultrasound equipment and staff able to conduct the examinations. These limitations were recognized as restricting physicians' ability to manage complications adequately during pregnancy and birth. Better availability of ultrasound was requested to improve obstetric management. Concerns were also raised regarding pregnant women's lack of knowledge and understanding of medical issues which could make counseling in relation to obstetric ultrasound difficult. Although the physicians perceived a positive attitude toward ultrasound among most pregnant women, occasionally they came across women who feared that ultrasound might harm the fetus.

    Conclusions: There seems to be a need to provide more physicians in antenatal care in Tanzania with ultrasound training to enable them to conduct obstetric ultrasound examinations and interpret the results themselves. Physicians also need to acquire adequate counseling skills as counseling can be especially challenging in this setting where many expectant parents have low levels of education. Providers of obstetric care and policy makers in Tanzania will need to take measures to ensure appropriate use of the scarce resources in the Tanzanian health care system and prevent the potential risk of overuse of ultrasound in pregnancy.

  • 712.
    Åhman, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Persson, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Edvardsson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Judith Lumley Centre, La Trobe University, Melbourne, Vic 3000, Australia.
    Lalos, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Graner, Sophie
    Small, Rhonda
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Two sides of the same coin - an interview study of Swedish obstetricians' experiences using ultrasound in pregnancy management2015Inngår i: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 15, artikkel-id 304Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The extended use of ultrasound that is seen in maternity care in most Western countries has not only affected obstetric care but also impacted on the conception of the fetus in relation to the pregnant woman. This situation has also raised concerns regarding the pregnant woman’s reproductive freedom. The purpose of this study was to explore Swedish obstetricians’ experiences and views on the role of obstetric ultrasound particularly in relation to clinical management of complicated pregnancy, and in relation to situations where the interests of maternal and fetal health conflict.

    Methods: A qualitative study design was applied, and data were collected in 2013 through interviews with 11 obstetricians recruited from five different obstetric clinics in Sweden. Data were analysed using qualitative content analysis.

    Results: The theme that emerged in the analysis ‘Two sides of the same coin’ depicts the view of obstetric ultrasound as a very important tool in obstetric care while it also was experienced as having given rise to new and challenging issues in the management of pregnancy. This theme was built on three categories: I. Ultrasound is essential and also demanding; II. A woman’s health interest is prioritised in theory, but not always in practice; and III. Ultrasound is rewarding but may also cause unwarranted anxiety.

    Conclusions: The widespread use of ultrasound in obstetric care has entailed new challenges for clinicians due to enhanced possibilities to diagnose and treat fetal conditions, which in turn might conflict with the health interests of the pregnant woman. There is a need for further ethical discussions regarding the obstetrician’s position in management of situations where maternal and fetal health interests conflict. The continuing advances in the potential of ultrasound to impact on pregnancy management will also increase the need for adequate and appropriate information and counselling. Together with other health care professionals, obstetricians therefore need to develop improved ways of enabling pregnant women and their partners to make informed decisions regarding pregnancy management.

  • 713.
    Åkerman, Sune
    et al.
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Högberg, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Andersson, Tobias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Survival of orphans in nineteenth-century Sweden1996Inngår i: Orphans and foster-children: a historical and cross-cultural perspective / [ed] Lars-Göran Tedebrand, Umeå: Umeå universitet , 1996, s. 83-105Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 714.
    Ödmark, Inga-Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hormone replacement therapy: benefits and adverse effects2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Numerous studies have shown that estrogen replacement therapy (ERT) is an effective treatment for vasomotor symptoms, insomnia and vaginal dryness. Beneficial effects have also been shown on lipid patterns and on the incidence of osteoporotic fractures. As ERT increases the risk of endometrial adenocarcinoma, combinations with various progestogens have been developed in order to protect the endometrium. However, the addition of progestogens tends to reduce the beneficial effects of estrogens on mood, cognition and lipid metabolism. The added progestogen often causes side effects such as irritability and depression. There is evidence that the effect on wellbeing varies between women and with the type of progestogen used. Women who prefer to avoid withdrawal bleedings can be given continuous combined hormone replacement therapy (HRT). Unfortunately, irregular bleedings are common at the beginning of treatment and reduces compliance. Recently, several studies have reported an increased risk of breast cancer and venous thrombosis, and therefore long-term treatment with HRT for women without climacteric symptoms is no longer recommended. The ongoing debate has, for the time being, resulted in a recommendation that improving quality of life (QoL) by treatment of climacteric symptoms should be the only indication for prescribing HRT.

    Aims and methods: The aims of the study were to investigate bleeding patterns, changes in wellbeing at onset and during long-term treatment, and lipid and lipoprotein profiles with two different types of continuous combined HRT. In addition, women starting, and women switching from mainly sequential HRT were compared. The design was a randomised, double-blind, one year, prospective, multicentre study including 249 healthy postmenopausal women who were given continuous daily oral treatment with either combined 0.625mg conjugated estrogen (CE) and 5mg medroxyprogesterone acetate (MPA) or combined 2mg 17β - estradiol (E2) and 1mg norethisterone acetate (NETA). Bleedings, if any, were recorded daily throughout the study. The main outcome measures (changes in wellbeing and climacteric symptoms) consisted of daily ratings of 12 items on a validated symptom scale. Serum concentrations of lipids and lipoproteins were measured at baseline and after one year of treatment.

    Results and conclusions: The majority of drop-outs were confined to the first three months, and the main reasons were bleedings and/or decreased wellbeing. Drop-outs were three times more common in the E2/NETA group. During the first month, 67% of the women reported irregular bleedings. The number of bleeding days decreased on both treatments during the first four months. Treatment with CE/MPA resulted in less irregular bleedings and a shorter time to amenorrhoea compared to E2/NETA.

    As expected, "starters" experienced more sweats than "switchers" at the onset of treatment, but both groups improved significantly. Side effects such as breast tenderness, swelling, depression and irritability appeared during the first treatment week in both groups. The side effects of HRT appeared much more quickly than the benefits and were more frequent in women with a history of premenstrual syndrome (PMS). Breast tenderness was more common in the E2/NETA group throughout the whole study period. Apart from that, there were no differences between the two treatment regimens as regards effects on well-being at the end of the study.

    Lipoprotein(a) levels, an important risk factor for cardiovascular disease, decreased in both treatment groups. Triglyceride levels increased in women treated with CE/MPA, and levels of total cholesterol, high density lipoprotein and low density lipoprotein fell in the E2/NETA group.

    In conclusion, treatment with E2/NETA caused more bleeding problems than treatment with CE/MPA. CE/MPA was better tolerated than E2/NETA at the beginning of the study, but among the women remaining in the study there was no difference in QoL between the two treatment groups. HRT counselling should take into account that a history of PMS increases the likelihood of side effects and that these may precede any beneficial effects. Both treatments produced beneficial effects on lipid and lipoprotein levels, and neither of the regimens was superior in this respect.

  • 715.
    Ödmark, Inga-Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Englund, Doris
    Risberg, Björn
    Jonsson, Björn
    Olsson, Sven-Eric
    Endometrial safety and bleeding pattern during a five-year treatment with long-cycle hormone therapy2005Inngår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 12, nr 6, s. 699-707Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To determine compliance, the incidence of untoward effects, and endometrial safety in postmenopausal women treated with 3-month sequential hormone therapy for up to 5 years.

    Design: A prospective, uncontrolled multicenter study of 129 women treated with 0.625 mg conjugated estrogens daily plus 10 mg medroxyprogesterone acetate for 14 days every third month. Endometrial biopsy samples were taken before the initiation of the study and then yearly during the next 5 years. Bleeding patterns were recorded.

    Results: Upon completion of the first 12 months of treatment, 76 of 126 biopsied women (60%) had secretory endometrium. After 5 years, this finding was reversed in biopsy specimens completed by 59 women, among whom 32 (56%) had insufficient or atrophic endometrium.We did not find any hyperplasia when the biopsy specimen was taken according to the protocol. One endometrial cancer was found by biopsy after 12 months, but the subsequent hysterectomy showed no sign of cancer. Ultrasound determinations of mean endometrial thickness during therapy showed a thin endometrium (mean = 4 mm, range = 1-13 mm). Amenorrhea was reported by 6.2% of 129 women after 12 months of treatment. Among the 59 women who completed the study, 71.2% had regular bleeding patterns every third month, 25.4% reported amenorrhea, and 3.4% had irregular bleeding patterns.

    Conclusions: The addition of 10 mg of medroxyprogesterone acetate for 14 days every third month to treatment with 0.625 mg of conjugated estrogens daily was well tolerated, and was associated with high endometrial safety.

  • 716.
    Ödmark, Inga-Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Haeger, Magnus
    Jonsson, Björn
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Effects of continuous combined conjugated estrogen/medroxyprogesterone acetate and 17beta-estadiol/norethisterone acetate on lipids and lipoproteins2004Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 48, nr 2, s. 137-146Artikkel i tidsskrift (Fagfellevurdert)
  • 717.
    Ödmark, Inga-Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jonsson, B
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Long-term effects of two different continuous combined regimens of hormone replacement therapy on well-being2004Inngår i: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 18, nr 6, s. 305-317Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Our aim was to compare the effect on well-being of two different continuous combined hormone replacement therapies (HRT) in women starting treatment (‘starters’) and women switching from mainly sequential HRT (‘switchers’). The design was a randomized, double-blind, 1-year, prospective study, including 249 postmenopausal women treated with 0.625 mg conjugated estrogen (CE)/ 5 mg medroxyprogesterone acetate (MPA) or 2 mg estradiol/1 mg norethisterone acetate (NETA) continuously. The main outcome measure was well-being, reported daily on a validated symptom scale during treatment cycles 1, 2, 6 and 13. Both treatment groups, starters and switchers, improved significantly in episodes of sweating during the first 6 months (p50.05). Women treated with estradiol/NETA experienced more breast tenderness compared to women using CE/MPA during the whole study period (p50.001), whereas there were no differences in negative mood symptoms between treatment groups. Starters experienced improved wellbeing during the whole study, whereas switchers experienced a transient improvement during the first 2 months. Overall, negative mood symptoms were more frequently reported by women with a history of premenstrual syndrome (PMS) (p50.05). Progestogen side-effects were more pronounced with estradiol/NETA than with CE/MPA combinations. Individual factors, such as previous PMS and previous HRT use, should be taken into consideration when prescribing HRT.

  • 718.
    Ödmark, Inga-Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jonsson, Björn
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Well-being at onset of hormone replacement therapy: comparison between two continuous combined regimens2004Inngår i: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 7, nr 1, s. 92-102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To compare the effect on well-being of two continuous combined hormone replacement therapies (HRTs) in women starting treatment (‘starters’) and women switching from mainly sequential HRT (‘switchers’).

    Methods This was a randomized, double-blind, 1-month trial, in which 249 postmenopausal women were treated with either conjugated estrogen plus medroxyprogesterone acetate (CE/MPA 0.625 mg/5 mg) or 17β-estradiol plus norethisterone acetate (E2/NETA 2 mg/1 mg) continuously. Twelve items for measuring climacteric symptoms and well-being were reported daily on a validated symptom scale.

    Results Women taking CE/MPA reported lower scores for breast tenderness (p = 0.005), depression (p = 0.019), irritability (p = 0.004) and tension (p = 0.048), compared with women taking E2/NETA. Compared with pretreatment, both groups developed side-effects during the first week: breast tenderness, swelling and depression (p < 0.05). Starters, but also switchers, improved in sweats (p < 0.001 and p = 0.030). Compared with pretreatment ratings, switchers reported higher scores for breast tenderness (p < 0.001), depression (p = 0.050) and negative effects on daily life (p < 0.001), whereas starters reported only physical side-effects (p < 0.05). A history of premenstrual syndrome (PMS) predicted high scores for swelling (p = 0.023), depression (p = 0.024), tension (p = 0.009), irritability (p = 0.027), headache (p < 0.001) and negative effects on daily life (p < 0.001).

    Conclusions CE/MPA 0.625 mg/5 mg is better tolerated than E2/NETA 2 mg/1 mg, and starters react differently from switchers. Side-effects occur more quickly than benefits with HRT, and are more frequent in women with previous PMS.

  • 719.
    Ödmark, Inga-Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Carlström, Kjell
    Jonsson, Björn
    Jonasson, Aino Fianu
    Conjugated estrogen/progestagen versus tibolone hormone replacement therapy in postmenopausal women: effects on carbohydrate metabolism and serum sex hormone-binding globulin2006Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 53, nr 1, s. 89-96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To study the effects of different types of continuous hormone replacement therapy on carbohydrate metabolism.

    Method: Postmenopausal women were treated with conjugated estrogens, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5mg (CEE/MPA) or tibolone 2.5 mg daily for 13 28-day cycles. Serum glucose and insulin were measured before and during a 75 g oral glucose tolerance test (OGTT) at baseline and after 3, 6 and 13 cycles and areas under the curve (AUC) were calculated. Sex hormone-binding globulin (SHBG) was measured as an additional marker of nutritional and insulin status.

    Results: Neither CEE/MPA2.5 mg nor tibolone had any effects on carbohydrate metabolism whileAUCinsulin, AUCglucose and also body mass index (BMI) increased after 13 cycles of treatment in the CEE/MPA 5 mg group. SHBG increased significantly during CEE/MPA treatment and decreased significantly during treatment with tibolone. The effects on SHBG were less pronounced in the CEE/MPA 5 mg group. Pretreatment SHBG showed significant negative correlations to BMI and to variables that may reflect a certain degree of insulin resistance, the most pronounced being fasting glucose. Changes in SHBG during treatment with tibolone were negatively correlated to pretreatment SHBG and positively to BMI, AUCinsulin and fasting insulin resistance index, while no such correlations were found in the CEE/MPA groups. There were no correlations between changes in AUCinsulin and AUCglucose on one hand and basal variables or treatment SHBG on the other in the CEE/MPA groups.

    Conclusion: The effects of tibolone and CEE/MPA on carbohydrate metabolism were considered to have clinical significance only for CEE/MPA 5 mg, indicating a less favourable role of the higher progestagen dose. The results further support the important role of metabolic and insulin status in the physiological regulation of SHBG and also indicate that the suppressive effect of tibolone on circulating SHBG is mainly depends on pretreatment SHBG levels. SHBG does not reflect changes in carbohydrate metabolism during CEE/MPA treatment.

  • 720. Ödmark, Inga-Stina
    et al.
    Jonsson, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bleeding patterns in postmenopausal women using continuous combination hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate or with 17β-estradiol and norethindrone acetate2001Inngår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 184, nr 6, s. 1131-1138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: We studied bleeding patterns in postmenopausal women who were using 2 types of continuous combination regimens.

    STUDY DESIGN: A prospective, double-blind, randomized study of 208 postmenopausal women treated with conjugated estrogen, 0.625 mg, and medroxyprogesterone acetate, 5 mg, or with 17beta-estradiol, 2 mg, and norethindrone acetate, 1 mg.

    RESULTS: The mean number of bleeding days decreased during the first 4 months of treatment (P <.002) but not thereafter. The number of bleeding days was fewer (P <.002) and the time until amenorrhea was shorter (P <.02) in patients receiving conjugated estrogen and medroxyprogesterone acetate than in patients receiving 17beta-estradiol and norethindrone acetate. The odds ratio for progression to amenorrhea with the use of conjugated estrogen and medroxyprogesterone acetate was 1.58, in comparison with the use of 17beta-estradiol and norethindrone acetate. A thick endometrium at the start of treatment resulted in more bleeding days than were found for a thin endometrium (P <.03). Body mass index, age, and blood pressure had no predictive value for bleeding problems.

    CONCLUSIONS: Treatment with continuous combined conjugated estrogen and medroxyprogesterone acetate resulted in fewer bleeding problems than did treatment with 17beta-estradiol and norethindrone acetate. Endometrial thickness may help to predict the chance of achieving amenorrhea during early hormone replacement therapy.

  • 721.
    Öfverman, Charlotte
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Obstetrik och gynekologi.
    Progesterone metabolites: learning, tolerance, antagonism & metabolism2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Progesterone metabolites as allopregnanolone, isoallopregnanolone and tetrahydrodeoxy-corticosterone (THDOC) are increased in the luteal phase of the menstrual cycle, throughout pregnancy and during stress. Allopregnanolone and THDOC are neurosteroids with 3α-hydroxy, 5α-configurations and positive modulating effect on the GABAA receptor. They have similar properties and effect, and share the same binding sites on the GABAA receptor. Isoallopregnanolone has a 3β-hydroxy, 5α-configuration and a diverse effect as a proposed antagonist to both allopregnanolone and THDOC. Neurosteroids are thought to exert their effect predominantly at extrasynaptic GABAA receptors, containing for example α4- or α5-subunits. Such receptors are involved in the tonic response. Different subunits have diverse distribution pattern in the brain and are involved in different functions. The α5-subunit, mainly expressed in the hippocampus, is involved in learning, while α4 is more widespread and involved in e.g. anxiety and anaesthesia.

    The aim of the present thesis was to contribute to the knowledge about selected progesterone metabolites and their effects on learning and tolerance development, as well as their metabolism. Also basic characteristics between different α-subunits of the GABAA receptor were evaluated.

    The thesis shows that the effect of bicuculline and pentobarbital is not dependent on the α-subunit isoform of the GABAA receptor expressed in oocytes. Acute tolerance developed after allopregnanolone-induced anaesthesia with a decrease at both mRNA and protein levels of the GABAA receptor α4-subunit in the thalamus VPM nucleus. A negative correlation between the α4 mRNA and the increased dose of allopregnanolone needed to maintain the anaesthesia level was also shown. In addition, allopregnanolone induces a learning impairment in the Morris water maze test, when high concentrations of allopregnanolone are present in the brain. This impairment is not possible to reverse by isoallopregnanolone. In α5β3γ2L-transfected HEK-293 cells THDOC induces a baseline shift of its own and also potentiate the GABA-current. Neither of those THDOC effects can be inhibited by isoallopregnanolone. Instead isoallopregnanolone shows an agonistic effect on the THDOC-potentiation of the GABA-response. The main allopregnanolone metabolites identified, 5α-DHP and isoallopregnanolone, as well as allopregnanolone itself are mainly localized to the brain after an i.v. injection. After an isoallopregnanolone injection there is a more even distribution of the given steroid and the metabolites between plasma and brain. There is an epimerisation between isoallopregnanolone and allopregnanolone and vice versa.

    In conclusion, the present thesis shows that the α4-subunit in the thalamus VPM nucleus is likely to be involved in the acute tolerance development against allopregnanolone and that allopregnanolone-induced learning impairment is likely to be hippocampus dependent. The lack of antagonistic effect of isoallopregnanolone on the THDOC-induced α5β3γ2L-GABAA response, together with epimerisation of isoallopregnanolone to allopregnanolone, could explain why isoallopregnanolone does not work as an antagonist to the allopregnanolone-induced learning impairment in a hippocampus dependent learning task.

  • 722.
    Öfverman, Charlotte
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hill, Martin
    Institute of Endocrinology, Nároni trída 8, CZ 116 94 Prague, Czech Republic.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Inga-Maj
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Neurosteroid metabolism: identification of allopregnanolone and isoallopregnanolone metabolites in rat brain and plasmaManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Metabolism of progesterone produces steroids that by themselves have other functional properties than the hormone. The most prominent metabolite, allopregnanolone (3α-OH-5α-pregnane-20-one), has a strong GABAA receptor agonistic activity. Isoallopregnanolone (3β-OH-5α-pregnane-20-one) is also formed from progesterone; this allopregnanolone epimer can in certain situations function as an antagonist to effects induced by allopregnanolone.

    This study was designed to further evaluate the metabolism of allopregnanolone and isoallopregnanolone in the rat. This was done by intravenous injections of either steroid and analyses of selected possible metabolites within the brain as well as in plasma, eight minutes after the injection. Analyses were performed with GC-MS.

    It was found that the main metabolites accumulated after the allopregnanolone treatment was the precursor 5α-dihydroprogesterone, followed by isoallopregnanolone. The injected allopregnanolone, as well as the two major metabolites formed, were mainly present in the brain. When isoallopregnanolone was injected, the main metabolites formed were allopregnanolone and 6α-hydroxylated isoallopregnanolone, followed by the precursor 5α-dihydroprogesterone. Interestingly, the metabolites formed after isoallopregnanolone injections were more evenly distributed between the analyzed brain areas and the plasma. After both treatments a high proportion of conjugation (typically around 50%), was in plasma found for both the injected and the produced steroids.

    With the high amounts of metabolites found in the brain, there might be a high converting capacity within the brain for these kinds of steroids. This suggests that interchange between the studied epimers is of physiological nature. One may then speculate that the brain uses the conversion between allopregnanolone and isoallopregnanolone to regulate the GABAergic inhibition. If this is the case, a dysregulation of this metabolism might cause symptoms and/or CNS disorders. 

  • 723.
    Öfverman, Charlotte
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Strömberg, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Birzniece, Vita
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Turkmen, Sahruh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hill, Martin
    Institute of Endocrinology, Nároní trída 8, CZ 116 94, Prague, Czech Republic.
    Lundgren, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Inga-Maj
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The progesterone metabolite isoallopregnanolone is a subunit-selective antagonist of the GABA-A receptorManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

     Allopregnanolone is a progesterone metabolite that can negatively affect learning and induce anaesthesia in rats. It also impairs episodic memory in women. Allopregnanolone levels are elevated during the luteal phase of the menstrual cycle, during pregnancy, and during stress. Allopregnanolone is a strong positive modulator of the GABAA receptor. The subunit composition of the GABAA receptor is of importance for effects of modulators, and GABAA receptors including the α5-subunit are of significance for learning, while receptors with other subunits are involved in e.g. anesthesia. Isoallopregnanolone, a natural 3β-epimer of allopregnanolone, has been shown to antagonize allopregnanolone-induced anesthesia in rats.

    We tried to block the allopregnanolone-induced impairment of learning in rats in the Morris water maze test, using isoallopregnanolone (4–32 mg/kg). We also determined steroid concentrations in blood and brain tissue, and with whole-cell patch clamp we studied the effects of isoallopregnanolone and tetrahydrodeoxycorticosterone (a neurosteroid similar to allopregnanolone) on HEK-293 cells expressing the human α5β2γ2L GABAA receptor.

    Isoallopregnanolone did not block the negative effects of allopregnanolone (2 mg/kg) in the Morris water maze test. Our presumed antagonist actually had an agonistic effect on the tetrahydrodeoxycorticosterone-mediated potentiation of the GABA effect on the α5β2γ2L GABAA receptor. The baseline shift induced by tetrahydrodeoxycorticosterone alone was not reversed by isoallopregnanolone. A bidirectional epimerisation between allopregnanolone and isoallopregnanolone was also identified in the rat.

    The lack of antagonistic effect at the α5β2γ2L GABAA receptor together with the epimerisation of isoallopregnanolone to allopregnanolone would probably explain the lack of effect of our proposed antagonist on the allopregnanolone-induced impairment of learning 

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