Preeclampsia is a placental-related disorder characterized by generalized endothelial activation. Vascular predisposition is associated with the occurrence of preeclampsia and the recurrence risk is substantial. Onset of preeclampsia is preceded by placental hypo-perfusion, and placental over-production of vasoconstrictive agents might explain symptoms such as hypertension and proteinuria. Preeclampsia is associated with the birth of small-for-gestational-age (SGA) infants. The trajectory of postnatal growth in SGA-born children is described as catch-up, but it is unclear whether prenatal preeclampsia is independently associated with postnatal growth. The objectives were: firstly, to study the association between partner change and prior miscarriages on the occurrence of preeclampsia and SGA; secondly, to study postnatal growth in children prenatally exposed to preeclampsia; and thirdly, to address the association between blood pressure (BP) changes during pregnancy and risks of preeclampsia and SGA. Population-based cohort studies were performed with information from the following registers: Swedish Medical Birth Register, Uppsala Mother and Child Database and Stockholm-Gotland Obstetric Database. Associations were estimated with logistic and linear regression analyses, with adjustments for maternal characteristics, including body mass index, pre-gestational diseases and socioeconomic factors. The results were, firstly, that partner change was associated with preeclampsia and SGA birth in the second pregnancy but depended on the outcome of the first pregnancy, and that a history of recurrent miscarriages was associated with increased risks of preeclampsia and SGA. Secondly, prenatal exposure to preeclampsia was associated with increased offspring growth in height during the first five years. This association was also seen in children born with normal birth weight for gestational age. Thirdly, pre-hypertension in late gestation and elevated diastolic BP from early to mid-gestation were both associated with SGA birth. Further, women with pre-hypertension in early gestation without lowered diastolic BP until mid-gestation seemed to represent a risk group for preeclampsia. To conclude, the importance of previous pregnancy outcomes in the antenatal risk evaluation was highlighted. Secondly, the results imply that postnatal growth trajectory is related to maternal preeclampsia, in addition to SGA. Thirdly, the association between BP changes within a normal range and SGA may challenge the clinical cut-off for hypertension in pregnancy.

Background Advances in medical treatment during the last 50 years have resulted in more individuals with congenital heart disease (CHD) and Marfan syndrome reaching childbearing age. The substantial physiological changes during pregnancy result in a high-risk situation, and pregnancy is a major concern in women with these conditions. Aims To describe the socio-demographic characteristics, birth characteristics and reproductive patterns of individuals with CHD and women with Marfan syndrome. To investigate obstetric and neonatal outcomes in the firstborn children of individuals with CHD and women with Marfan syndrome. To study long-term cardiovascular outcomes after childbirth in women with Marfan´syndrome. Methods The studies are population-based register studies. The study population in the first paper included all women born between 1973 and 1983 who were alive and resident in Sweden at the age of 13 (494 692 women, of whom 2 216 were women with CHD). In the second paper, the same definition of the study population was chosen, except that it involved all men born between 1973 and 1983 (522 216 men, of whom 2 689 men with CHD). The third and fourth papers involved a study population of all Swedish women born between 1973 and 1993 who were still living in Sweden at age 13. This population consisted of 1 017 538 women, 273 of whom had been diagnosed with Marfan syndrome. Results and conclusions The individuals studied were more often born preterm, and were small-for-gestational age babies. They were more likely to have been born by cesarean section. In women with CHD, these characteristics were repeated in their firstborn children. No increased risks were found in children of men with CHD or in children of women with Marfan syndrome. There was no increased risk of aortic dissection in women with Marfan syndrome during pregnancy compared to women with Marfan syndrome who did not give birth. Higher frequencies of cardiac arrhythmia and valvular heart disease were found after childbirth in women with Marfan syndrome. Pregnancy in women with CHD is a high-risk situation associated with increased risk of adverse neonatal outcomes for the expected child. Pregnancy in women without CHD, but where the father has CHD is not so associated with increased risk of adverse obstetric or neonatal outcomes. Pregnancy in women with Marfan syndrome is not associated with adverse outcomes for the expected child.

Background: Although giving birth is a positive experience for many, some 10% of pregnant Swedish women suffer from severe fear of childbirth (FOC), which impairs their daily functioning and poses a risk for a negative delivery experience. This thesis focuses on the mental and health-economic effects of severe FOC, and explores new treatment options for childbirth-related anxiety. Aims: (i) to investigate the prevalence of and variables associated with severe FOC, (ii) to estimate the cost of illness of severe FOC and (iii) to explore whether Internetbased cognitive behaviour therapy (ICBT) is feasible for treating pregnant women with severe FOC and those with childbirth-related symptoms of posttraumatic stress disorder (PTSD). Design and Results: Study 1: In a cross-sectional study 1635 pregnant women were asked about their FOC via the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), and provided socio-demographic data and information of their preferred mode of delivery. It was found that 15.6% of the participants had a severe FOC, which also strongly correlated with the preference of a caesarean section. Study 2: In a prospective case-control cohort study we mapped all visits, in-patient care, sick leave and delivery variables from medical records and estimated the societal costs in two groups of women; one group with severe FOC and one with low FOC. The costs for the group with severe FOC were 38% higher than for the low FOC group. Study 3: Twenty-eight nulliparous women with severe FOC were self-recruited to an eight weeks ICBT program for severe FOC. Fifteen women followed the entire program. Their FOC decreased significantly after treatment (Cohen’s d=0.95, p<0.0001), which means that ICBT is feasible and an option for treating women with severe FOC. Study 4: Fifteen participants in Study 3 wrote narratives of the imminent delivery before as well as after therapy. After treatment, the women had a more realistic attitude towards childbirth, more self-confidence and more active coping strategies. Partners and staff were perceived as more helpful, and the women were more aware of the child they were bearing. Study 5: Fifty-six women with a traumatic delivery experience were included in a randomized wait-list controlled study (RCT) of the effects of an eight week long ICBT program for childbirth-related PTSD symptoms. These symptoms decreased in both groups during active therapy, while the between-group effect size varied depending on measurements. Psychiatric comorbidity decreased in both groups after active treatment. Conclusion: Severe FOC is prevalent among Swedish pregnant women, and the cost of illness of this marker of peripartum psychological vulnerability is considerable when treated using standard care. A new treatment option for this group with ICBT seems feasible and is associated with more realistic attitudes towards the imminent delivery. An RCT with eight weeks of ICBT for parous women with PTSD symptoms also had promising results. As severe FOC is prevalent and associated with mental and economic burdens for the individual and the society, there is an urgent need to expand the research field. It is important to find feasible and effective treatments that can be applied on a large scale. / Denna avhandling undersöker (i) hur vanligt det är att svenska gravida kvinnor lider av rädsla för förlossningen, och (ii) hur detta påverkar kvinnornas sjukvårdskonsumtion under denna period samt vilka kostnader detta innebär för samhället; testar och utvärderar (iii) nya behandlingsmetoder för rädsla för förlossningen och för posttraumatiska stressymptom efter en traumatisk förlossning. Avhandlingen består av fem delstudier: Studie 1 var en studie bland 1635 gravida kvinnor och visade att mer än var tionde gravid kvinna har svår förlossningsrädsla. Denna hade samband med kvinnornas önskemål om planerat snitt som förlossningssätt, och hos omföderskor, med tidigare negativa upplevelser av förlossningen. Studie 2 jämförde sjukvårdskonsumtion och sjukskrivning under graviditet och den första tiden efter förlossningen hos förstföderskor med svår respektive lindrig förlossningsrädsla, vilka omhändertagits i den ordinarie förlossningsvården. Gruppen med svår förlossningsrädsla visade sig ha avsevärt högre kostnader orsakade av att de i genomsnitt hade högre sjukskrivningstal under graviditet och fler besök på grund av psykiska besvär, samt oftare förlöstes med kejsarsnitt och hade komplicerade förlossningar. I Studie 3 testade 28 förstföderskor med svår förlossningsrädsla en ny behandlingsmetod med kognitiv beteendeterapi (KBT) via internet. Behandlingen medförde att kvinnornas rädsla kraftigt minskade från företill efter behandling. I Studie 4 skickade 15 av kvinnorna i Studie 3 in berättelser via nätet om hur de föreställde sig att deras förlossning skulle bli, såväl innan terapin startade som när den var avslutad. Efter genomförd terapi hade kvinnorna en mer realistisk attityd till förlossningen än före terapin och visade tecken på att ha ett bättre självförtroende och mer aktiva strategier att hantera den kommande förlossningen. Studie 5 utforskade om kvinnor, som upplevt en traumatisk förlossning, kan bli hjälpta av behandling med KBT via internet. Traumatiserade kvinnor slumpades till att antingen få behandling direkt eller få behandlingen efter en väntetid (kontrollgruppen). I båda grupperna minskade kvinnornas posttraumatiska stressymtom, liksom förekomsten av depression och andra ångestproblem. Sammanfattning: Avhandlingen visar att svår förlossningsrädsla är vanligt förekommande och medför lidande för kvinnor och ökade kostnader för samhället i samband med graviditet och förlossning, när detta problem hanteras i den vanliga vården. Två internetbaserade studier testar kognitiv beteendeterapi som behandling för svår förlossningsrädsla och för problem efter en traumatisk förlossning och visar att dessa behandlingsformer tycks fungera väl och i framtiden skulle kunna utgöra ett alternativ som medför att vård görs tillgänglig också för kvinnor som inte har tillgång till kvalificerade hjälpinsatser på andra sätt. Svår förlossningsrädsla och ångestproblem efter en traumatisk förlossning föreligger ofta tillsammans med annan psykisk sjuklighet varför diagnostik och behandling behöver utföras av personer med tillräcklig kompetens för dessa uppgifter. Otillräckligt behandlad/icke behandlad svår förlossningsrädsla ökar riskerna för att kvinnan upplever en kommande förlossning som traumatisk. Avhandlingens slutsatser behöver undersökas i fler och större studier, och, avseende behandlingsstudierna, i undersökningar som har tillräckligt stora kontrollgrupper. Om sådana studier bekräftar dessa preliminära fynd, blir frågan om screening för svår förlossningsrädsla aktuell eftersom det då finns såväl bra screeninginstrument som behandling som skulle kunna göras tillgänglig för stora grupper. Kommer samhället i denna situation att ha råd att inte försöka förebygga individuellt lidande och stora merkostnader för kvinnor med svår förlossningsrädsla? / Tämän tutkimuksen tavoitteena on tutkia (i) kuinka yleinen synnytyspelko on ruotsalaisten raskaana olevien naisten keskuudessa ja (ii) kuinka se vaikuttaa heidän terveyden‐ ja sairaanhoitopalveluiden kulutukseen raskauden aikana ja sen jälkeen, sekä selvittää miten synnytyspelko vaikuttaa yhteiskunnan kustannuksiin; kehittää, testata ja arvioida (iii) uusia hoitomuotoja synnytyspelon sekä synnytyksestä johtuvien psykologisen trau man (posttraumaattinen stressi, PTSD) hoitoon.' Tämä väitöskirja koostuu viidestä osatyöstä: 1. Ensimmäinen osatyö tutki synnystyspelon yleisyyttä 1635 raskaana olevan naisen keskuudessa. Tutkimus osoitti että joka seitsemäs raskaana oleva nainen Ruotsissa kärsii vakavasta synnytyspelosta. Keisarinleikkaus toiveen takana on usein vakava synnystyspelko. Uudelleen synnyttäjillä synnytyspelkoon vaikuttaa myös aiempi traumaattinen synnytyskokemus. 2. Toisessa osatyössa verrattiin ensisynnyttäjien terveyden- ja sairaanhoitokustannuksia sekä sairaslomapäiviä raskauden aikana, synnyksen yhteydessä sekä sitä seuraavan kolmen ensimmäisen kuukauden aikana. Vertailuryhmät seurasivat tavallista äitiysneuvolaohjelmaa, ryhmistä toisella oli vakava ja toisella lievä synnytyspelko. Vakavasta synnytyspelosta kärsivien naisten terveyden ja sairaanhoitopalvelujen käyttö osoittautui huomattavasti korkeammaksi kuin vertailuryhmässä. 3. Kolmannessa osatyössa 28 vakavasta synnytyspelosta kärsivää ensisynnyttäjää, testasi uutta ratkaisukeskeiseen terapiaan (KBT) pohjautuvaa Internetin kautta ohjattua psykologista hoito-ohjelmaa. Hoito lievensi huomattavasti osallistujien synnytyspelkoa. 4. Neljännessä osatyössä 15 naista (edellisestä osatyöstä 3) kirjoittivat osana terapiaansa kertomuksen tulevan synnytyksensä odotuksista. Sama tehtävä kertautui ennen terapian alkua sekä sen jälkeen. Kertomusten yhtäläiset teemat tunnistettiin minkä jälkeen ennen ja jälkeen hoitoohjelmaa kirjoitettujen kertomusten teemoja vertailtiin. Hoidon jälkeen naisten odotukset pohjautuivat suuremmassa määrin tietoon, he kuvailivat itsensä varmemmiksi sekä paremmin  valmistautuneiksi tulevaa synnytystä ajatellen. 5. Viides osatyö tutki Internetin kautta ohjatun ratkaisukeskeisen terapian (KBT) vaikutusta naisiin jotka kärsivät synnytyksen jälkeisestä henkisestä traumasta. Naiset satunnaistettiin tutkimuksessa joko välittömän hoidon ryhmään tai odotuslista ryhmään, joka sai saman hoidon myöhemmin. Hoidon jälkeen PTSD oireet vähenivät sekä hoitoettä kontrolliryhmässä. Myös masentuneisuus ja ahdistusoireet väheniväthoidon myötä. Yhteenvetona voidaan oheisista tutkimuksista todeta että synnytyspelko on yleinen ruotsalaisten raskaana olevien naisten keskuudessa. Synnytyspelko aiheuttaa kärsimystä sekä raskaana olevalle naiselle mutta myös lisäkustannuksia yhteiskunnalle. Kahdessa Internetin kautta ohjatussa ratkaisukeskeisessä hoito-ohjelmassa testattiin uusia hoitomuotoja raskaana oleville ensisynnyttäjille sekä synnytyksen jälkeisistä traumaoireista kärsiville naisille. Tulokset osoittavat, että Internetin kautta ohjattu hoito toimii näissä ryhmissä hyvin ja saattaisi tulevaisuudessa olla vaihtoehto kohderyhmille, joille sopivaa terapeuttista hoitoa nykytilanteessa ei voida tarjota. Koska vaikea synnytyspelko ja synnytystä seuraavat PTSD oireet esiintyvät usein muiden mielialahäiriöiden rinnalla, on tärkeää, että näitä naisia hoitavalla henkilökunnalla on tarpeellinen pätevyys hoitaa myös mielenterveysongelmia. Hoitamatta jätetty tai puutteelisesti hoidettu synnytyspelko lisää raskaana olevan naisen riskiä kokea synnytyksensä traumaattisena. Tulevissa tutkimuksissa tämän tutkimusprojektin tulokset ja johtopäätökset on syytä toistaa useammissa ja ennen kaikkea suuremmissa ryhmissä. Jos tutkimustemme alustaville tuloksille löytyy tukea, nousee kysymys synnystyspelon seulonnasta äitiysneuvoloissa ajankohtaiseksi; sekä seulontamenetelmä että tehokas hoitotapa ovat olemassa ja voitaisiin tarjota suuremmille kohderyhmille. Onko yhteiskunnalla sellaisessa tilanteessa varaa olla ennaltaehkäisemättä synnystyspelkoisten naisten kärsimystä?

Many young women today are concerned about their sexual health; an increasing number of them consult gynaecologists, youth centres (YCs) and general practitioners with vulvar problems such as painful sensations associated with vaginal intercourse (VIC). It is known that some women continue to have VIC despite pain. Theoretically, repeated painful VIC might elicit vaginistic reactions, which may increase the pain and induce vicious circles. Since many clinicians and researchers nowadays notice that pain during VIC often starts at young age, it is important to investigate how pain during VIC starts and is maintained in younger populations. The overall aim of this thesis was to investigate young women’s experiences of ideal sexual situations and pain during VIC. Women aged 13-22 years participated in our studies, which used both quantitative (study I and IV) and qualitative (study II and III) methods. For paper I, a questionnaire was developed and used in a YC sample (n=300); informants for paper II were selected from that sample to participate in qualitative interviews (n=16). Another qualitative interview study for paper III with a complimentary research question was conducted in a different YC sample (n=14). For paper IV, a questionnaire was developed based on the results from study I, II and III to test the hypotheses derived from study II in a sample of female high school students (n=1566). The findings revealed that 65% of the women reported pain related to first VIC. Among those who reported VIC during the previous month, 49% had experienced pain and/or discomfort during VIC during that same period (paper I). In paper IV, 47% of the women reported experience of pain and/or discomfort during VIC, and among those, 47% continued to have VIC, 22% feigned enjoyment, and 33% omitted telling the partner about their pain. In paper II, the women’s reasons for continuing to have VIC despite pain were: striving to reach their ideal image of a woman, characterized as always willing to have VIC; being perceptive of their partner’s sexual needs; and being able to satisfy their partner. In paper IV the hypotheses derived from study II were confirmed and showed, for example that a significantly higher proportion of women who continue to have VIC despite pain than women who did not had difficulty refusing sex when the partner wants it, felt inferior to the partner during sex, regarded the partner’s satisfaction as more important than their own, felt dissatisfaction with their sex life, and feigned enjoyment despite pain. In a multivariate model, continuing to have VIC despite pain was associated with feelings of being inferior to the partner during sex (adjusted OR 1.82; CI 1.10-3.02), dissatisfaction with their own sex lives (adjusted OR 1.76; CI 1.14-2.72) and feigning enjoyment while having pain (adjusted OR 7.45; CI 4.37-12.69). The major reason for continuing to have VIC was that the partner’s enjoyment was prioritized higher than their own (paper IV). In paper III, we found that women without pain during VIC also felt pressure from social norms and demands and had experienced partners “driving their own race”. However, they managed to some extent to resist these unequal gender norms because of their urge to experience pleasure. In conclusion, pain during VIC is a common complaint among young Swedish women, and a high proportion of them continue having VIC despite pain. The women’s notion of prioritizing the partners´ enjoyment before their own illustrates that unequal gender regimes affect young women’s (hetero)sexuality negatively.

Ovarian steroid hormones are neuroactive steroids with widespread actions in the brain, and are thus able to influence mood, behavior and cognition. In this thesis the effects of progesterone withdrawal and the direct effects of the progesterone metabolite allopregnanolone are evaluated. Allopregnanolone, through binding to the GABAA receptor complex, enhances inhibitory neurotransmission, thus exerting anxiolytic, sedative and antiepileptic effects. The acoustic startle response (ASR) is a withdrawal reflex evoked by sudden or noxious auditory stimuli, and can be measured in humans as an eye blink. ASR is significantly increased in several anxiety disorders, and notably also during progesterone withdrawal. Sensorimotor gating can be assessed by measuring prepulse inhibition of the startle response (PPI). The CNS circuits regulating PPI are sensitive to hormone fluctuations. GABAergic drugs are involved in cognitive impairment and animal studies have indicated that allopregnanolone may inhibit learning. The main purpose of this research was to evaluate the behavioral effects of progesterone withdrawal on the startle response and sensorimotor gating in PMDD patients and healthy controls, in healthy third trimester pregnant women and healthy postpartum women. A second aim was to evaluate allopregnanolone effects on memory and cognition in healthy women and also on the startle response and PPI. We found that PMDD patients have an increased startle response across the menstrual cycle and a deficiency in sensorimotor gating during the late luteal phase. Ovarian steroids affect sensorimotor gating; pregnant women have lower levels of PPI than late postpartum women. Acutely administered allopregnanolone did not affect the ASR or PPI. Allopregnanolone impairs episodic memory in healthy women. In conclusion, our studies suggest that ovarian steroids, including allopregnanolone, do not influence the startle response. Ovarian steroids affect sensorimotor gating; pregnancy, a condition with high levels of ovarian steroids, suppresses PPI. Theoretically, the variability in PPI across reproductive events is due to effects mediated by the progesterone or estradiol receptors but is not mediated by allopregnanolone. PMDD patients display decreased PPI during the late luteal phase, suggesting underlying pathophysiology in common with other anxiety disorders. The most vulnerable memory system, the episodic memory, is impaired by the allopregnanolone in healthy women.

Vaginismus is a sexual pain disorder, where spasm of musculature of the outer third of the vagina interferes with intercourse. Vaginismus exists in two forms: total vaginismus, where intercourse is impossible, and the more seldom described partial vaginismus, in which intercourse is possible but painful. The aim of the thesis was to develop a useful definition of partial vaginismus for both clinical and scientific purposes; to describe the prevalence of partial vaginismus among women with superficial coital pain; to report on symptoms and clinical findings in women with partial vaginismus; and to present treatment results for women with vaginismus. In a clinical sample of 224 women with superficial coital pain, we found a great overlap of the clinical diagnoses of partial vaginismus (PaV) and vulvar vestibulitis (VVS) (nowadays called provoked vestibulodynia); 102 women had both PaV and VVS. All women with VVS had vaginismus. Partial vaginismus was more common in all our samples than total vaginismus. sEMG of pelvic floor muscles was found to be of no value in distinguishing women with partial vaginismus with or without vulvar vestibulitis (PaV+/-VVS) (n=47) from each other or from an asymptomatic group (n=27). Women with PaV+/-VVS (n=53) reported not only burning pain but also itch during a standardized penetration situation (sEMG of pelvic floor muscles), while asymptomatic women (n=27) did not. In most cases, the appearance of burning pain preceded the appearance of itch. In a retrospective interview study, 24 women with PaV+/-VVS reported pain after intercourse more often than pain during penetration at the onset of the problem. When the women ceased having intercourse, both symptoms were equally common. Intensity of pain during penetration increased dramatically from very low at onset of the problem to very high when the women ceased having intercourse, while intensity of pain after intercourse was already high at onset of the problem and increased to very high when the women ceased having intercourse. Pain after intercourse in women with PaV+/-VVS was described as burning and/or smarting and lasted in mean for two hours, while pain during penetration was described with words like sharp/incisive/bursting and lasted for one minute. At long-term follow-up (more than three years) of a group of women treated with cognitive behaviour therapy for vaginismus (n=59, response rate 44/59 on a questionnaire), a majority were able to have and enjoy intercourse. The proportion of women with positive treatment outcome was, however, associated to the definition of treatment outcome. An ability to have intercourse at end of therapy was maintained at follow-up. Every tenth women with vaginismus healed spontaneously after thorough assessment. Conclusion: Partial vaginismus was more common in our studies than total vaginismus, and all women with vulvar vestibulitis had partial vaginismus. Women with PaV+/-VVS reported not only burning pain during standardized penetration but also itch. When the problem started in women with PaV+/-VVS, pain after intercourse was more common than pain during penetration. Pain after intercourse was described as longlasting and burning and/or smarting, while pain during penetration was described as short and sharp/incisive/bursting. Long-term follow-up results of a series of women treated with CBT for vaginismus show good treatment outcome.

Background Screening by cytology has been highly effective in reducing the incidence and mortality from squamous invasive cervical cancer (ICC), but the effectiveness is less established regarding non-squamous ICC and regarding women above screening ages and below 30 years of age. Cervical cancer still occurs despite the presence of an organised screening programme. A substantial proportion of screened women with ICC are reported to have had previous abnormal cytology findings. The significance of negative cytology with limited evaluation is not quite determined, the most effective management of women with low-grade abnormalities is controversial, and evaluation of long-term effect of different treatment methods is limited. Aims To identify possible areas of improvements in the prevention of cervical cancer by evaluating the effectiveness of the Swedish cervical screening programme, and by exploring risk factors for ICC in the cytological screening histories and in the management of women with abnormal cytology findings. Methods The screening histories of all ICC cases in Sweden 1999-2001 (n=1230) and of five population-based control women per case were reviewed, using data from the Swedish Cancer Registry, the national population register, the Swedish national cervical screening quality register, histopathological reports and questionnaires to clinicians. The risk of cervical cancer according to screening histories 0.5-6.5 years before cancer diagnosis was estimated as odds ratios (ORs) in logistic regression models with 95% confidence interval (CI) (Paper I). Risk related to different cytological reports was assessed in women below 67 years of age with cytology (n=572, n=3569) in Paper II. The initial follow-up of women with abnormal or unsatisfactory cytology reports (n=159, n=258) was evaluated in Paper III, and further investigation and treatment of abnormalities (n=143 cases, n=176 controls) in Paper IV. Results The cancer cases were above screening ages (31%), had not been screened according to recommendations (33%), had negative cytology (23%), or had previous positive screening tests (13%). No screening within the recommended interval increased the risk of squamous (OR 2.97, 95% CI 2.51-3.50) as well as non-squamous cancer (OR 1.59, 95% CI 1.20-2.11), and increased the risk in all ages. Negative cytology with partially obscuring factors and unsatisfactory cytology increased the risk of subsequent early stage ICC. All cytological abnormalities increased the risk of ICC, and women with glandular atypia or atypia in cells of uncertain origin carried a particularly high risk (OR 11.69, 95% CI 7.02-19.46). After a low-grade squamous abnormal smear finding, further investigation with biopsy was more effective than repeated cytology (OR 0.46, 95% CI 0.24-0.89). Lack of biopsy increased the risk in women with both low-grade and high-grade squamous abnormalities. Neither repeat cytology, nor biopsy, decreased the risk in women with glandular atypia or atypia in cells of uncertain origin. Treatment decreased the risk, even when the biopsy before treatment was negative or showed low-grade atypia only. Ablative therapy was less effective than excision and laser conisation was the most effective therapy. Conclusions Improved adherence to screening recommendations and including older women at increased risk in the programme would have significant cancer preventive gains. Women with negative cytology with limited evaluation and with unsatisfactory cytology may need further evaluation. Assessment with biopsy should be recommended for women with low-grade as well as high-grade squamous abnormalities. The diagnosing of precancer lesions and the identification of women in need of treatment warrant improvements, in particular in cases of glandular or “other” atypia in cytology. Treatment techniques need further evaluation.

Background: Pelvic organ prolapse (POP) is a relatively common condition. In Sweden, the overall estimated prevalence of POP in the female population is 31% and the prevalence of symptomatic prolapse is 8–15%. The prevalence of POP increases with age. The lifetime risk of undergoing pelvic floor surgery is estimated to 11%. The aim of this thesis was to investigate outcomes of vaginal hysterectomy for treatment of prolapse; to study outcomes of cystocele repair surgery and patient satisfaction related to different anaesthesia methods; to explore women’s experiences of vaginal prolapse; and to investigate what is known regarding POP prior to surgery and healthcare-seeking behaviour. Methods: In the Swedish National Quality Register for Gynaecological Surgery (Gynop-register), 941 women were identified who underwent vaginal hysterectomy for prolapse from 1997 to 2005 and 1,364 women were identified who underwent cystocele repair surgery from 2006 to 2009. In-depth interviews were performed with 14 women with vaginal prolapse. Interview data were analyzed with a qualitative content analysis. To investigate women’s knowledge about POP and healthcare-seeking behaviour, a questionnaire was developed, validated and distributed to women with planned surgery for POP. Women undergoing hysterectomy or incontinence surgery were used as reference groups. Results: Severe complications after vaginal hysterectomy occurred in 3% of cases. Sexual activity was improved after vaginal hysterectomy, the number of women reported to have intercourse increased by 20% (p = 0.006). Subjective symptoms of urinary incontinence and overactive bladder were resolved in 50% of the women. De novo stress incontinence was reported by 11% of the women. Use of local anaesthesia (LA) in reconstruction of cystocele showed advantage over other forms of anaesthesia. Length of hospital stay, duration of use of postoperative pain-killing drugs, and time to return to daily activity were shorter among women who underwent surgery with LA compared to other forms of anaesthesia. Patient satisfaction was not related to methods of anaesthesia. In an interview study, the process from recognition the symptoms to seeking healthcare was highlighted. Two categories, “obstacles” and “facilitators” to seeking health care, were identified. One of the obstacles was lack of information on POP in the public domain. The main facilitators were feeling sexually unattractive and impaired physical ability due to POP. Some findings from the interview study were further explored in the questionnaire study. One out of five women with vaginal prolapse did not know that the symptoms were related to prolapse before consulting their physician. Over 30% of the women in the incontinence group were embarrassed to talk about incontinence, and they were unaware that it could be treated. The most frequent description of vaginal prolapse was vaginal bulging. Women in the prolapse group had significantly less access to information through brochures and public media than women in the incontinence group (p < 0.001). Conclusion: Short-term follow-up after vaginal hysterectomy showed that sexual activity and urinary symptoms had improved. Cystocele surgery using LA showed no disadvantage compared to surgery using other anaesthesia methods. POP surgery can therefore be performed safely with LA. Information on prolapse should be easily accessible to improve the possibility for women of gaining knowledge and thereby overcoming obstacles to seeking medical advice. Healthcare professionals have a significant role to play in informing women about symptoms and available treatment options.

Background: In high-income countries, hospital length of stay after a normal birth has gradually decreased correspondingly to length of stay in care of other patients. A short stay provides a greater opportunity for autonomy and an increased sense of participation, but it may involve great challenges satisfying parental guidance as well as on the possibility of preventing, discovering, and treating neonatal medical conditions. Aim: This study evaluates postnatal care based on cost calculations, risk assessments, and parents’ satisfaction with care. Methods: Questionnaires were sent to 1 122 new mothers and her partner during 1998-1999. For the summary of utilization of health care services during the first 28 days postdelivery, the participants were linked with registry data from the hospital administration system for mothers and newborns (n= 773). The answers were also used to describe new parents’ experiences with postnatal care (n = 1 479). The costs for five postnatal care models were estimated, including three care options: Maternity Ward, Family Suite, and Early Discharge. Data about neonatal readmissions and death within 28 days was retrieved from the Swedish Medical Birth Register, the Swedish Hospital Discharge Registry, and the Swedish Cause-of-Death Register between 1999 and 2002 (n = 197 898). This data was related to data about postnatal follow-up practices from all 48 Swedish delivery wards. Results: The readmission rate for the mothers was similar among the various care options, and there was no difference in utilization of health care or breastfeeding outcome due to type of maternity care. As a proxy for morbidity, the readmission rate for the newborns was influenced by postdelivery follow-up routines as routine neonatal examination timing. Depending on the proportion of mothers receiving care at the Maternity Ward, the costs differed significantly between the various care models, while parents’ preferences complied with the cost-minimizing option Family Suite. Most mothers and fathers (70%) were satisfied with the overall impression of the postnatal care, but 72% were dissatisfied with at least one particular topic. A main finding was that the parents experienced a close emotional attachment, an affinity that was not always supported by the staff. The father was not treated as a principal character even though the parents wanted the father’s to be involved and recognized. Conclusions: Since the postnatal care options are not always the most cost minimizing and postnatal routines influence neonatal morbidity and parental satisfaction, the postnatal services need to be improved. Without increasing risks or costs, every postnatal care option ought to meet the families’ need for support, security, autonomy, and attachment with each other.

Premenstrual depressive symptoms and mood swings affect 3-8% of women in fertile age. The female hormones are believed to be the cause. Progesterone is well studied, but estrogen is not, and either are other causes such as intimate partner violence and chronic stress. The aim in this thesis was to investigate the influence of hormones as well as psychological aspects on the most common problems among women seeking care for premenstrual symptoms. In a cross-sectional study, four groups of women were included: ongoing users of oral contraceptives, with or without adverse mood symptoms and previous users, with or without experience of adverse mood. Depression and anxiety were significantly more common in both groups with reported adverse mood, in comparison with their control groups with no adverse mood. Self-reported PMS was significantly more common in those women who reported adverse mood, however, there was no difference in prospectively defined PMS or PMDD between the two groups of previous users. In a RCT with 25 women completing the study, GnRH treatment were tested in combination with two different HRT add-back doses of estradiol, in combination with progesterone and placebo. The higher dose of estrogen 1.5 mg in combination with progesterone induced significantly more pronounced symptoms than in combination with placebo. The lower dose, 0.5 mg gave less symptom recurrence in combination with progesterone. Exposure to violence was investigated among PMDD patients, healthy controls and gynecological patients. Among the participating women, gynecological patients, reported physical and/or emotional abuse significantly more often than did PMDD patients, as well as healthy controls. Chronic stress was investigated with diurnal cortisol, and low-dose dexamethasone test.  There was no difference in diurnal secretion of cortisol between PMDD patients and controls. No difference in the degree of dexamethasone suppression was found between PMDD patients and controls. According to the results from these studies, the main symptom provoking factor in women with PMDD appears to be the estradiol and progesterone fluctuations across the menstrual cycle, whereas chronic stress and intimate partner violence appears to be less relevant.