Introduction: Obesity is a growing global public health problem and is as prevalent among pregnant women as in the general population. It is well known that obese women have an increased risk for several complications during pregnancy and delivery and this is also true for the neonate. Excessive gestational weight gain among obese women seems to further increase these risks for adverse outcomes. It has not been known up to the time of this study whether a behavioral intervention program designed for obese pregnant women could result in a reduction of gestational weight gain. Aim: The overall aim of the present thesis was to study the effect of an intervention program designed to control weight gain among obese pregnant women during pregnancy and to then observe the outcomes of their pregnancies. In addition we wanted to learn if this behavioral intervention program could result in a weight gain of less than seven kilograms. Material and methods: The intervention group consisted of 155 obese (BMI >30 kg/m2) pregnant women at the antenatal care clinic (ANC) in Linköping; the control group consisted of 193 obese pregnant women in two other cities. The women in the intervention group were offered, in addition to regular care at the ANC, motivational interviewing in weekly visits to support them in making this behavioral change. They were also offered aqua aerobic class once or twice a week. The women in the control group attended the routine antenatal program in their respective ANCs. Outcome measures were: weight in kg, pregnancy-, delivery and neonatal outcomes, prevalence of anxiety- and depressive symptoms and attitudes and experiences of participating in an intervention program. Results: The women in the intervention group had a significantly lower gestational weight gain and also had a lower postnatal weight than the women in the control group. The percentage of women in the intervention group who gained <7 kg was greater than the percentage in the control group. There were no differences between the two groups in pregnancy-, delivery- and neonatal outcomes. In addition, there was no difference in prevalence of symptoms of anxiety and depressions between the intervention- and control group and the gestational weight gain did not have any effect on symptoms of depression or anxiety. The women in the intervention group with gestational weight gain <7 kg, weighed less at the two years follow-up than the women in the control group. Most of the women who participated in the intervention program expressed positive attitudes and were positive towards their experiences with the intervention program and their efforts to manage the gestational weight gain. Conclusion: The intervention program was effective in controlling weight gain during pregnan-cy and did not change the pregnancy, delivery or neonatal outcomes or the prevalence of anxie-ty- and depressive symptoms. The group with a gestational weight gain <7 kg showed the same distribution of complications as the group with a higher weight gain. The intervention program seems to influence the development of weight in a positive direction up to two years after childbirth. The women were also satisfied with their participation in the intervention program.

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.

Psychological problems are common in infertile women undergoing in vitro fertilization (IVF) treatment.  The aim of this thesis was to determine the prevalence of psychiatric disorders, such as mood and anxiety disorders, and related risk factors and personality traits in women and men undergoing IVF. Participants were 1090 consecutive women and men, 545 couples, attending a fertility clinic in Sweden during a two-year period. The Primary Care Evaluation of Mental Disorders (PRIME-MD), based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), was used for evaluating mood and anxiety disorders. The participation rate was 862 (79 %) subjects. Any psychiatric disorder was present in 31 % of females and in 10 % of males. Major depression was prevalent in 11 % of females and 5 % of males. Only 21 % of the subjects with a psychiatric disorder had some form of treatment. A negative pregnancy test and obesity (BMI ≥ 30) were risk factors for mood disorders in women and the only risk factor for depression in men was unexplained infertility. Anxiety disorders were less common than in the general population and no IVF-related risk factors were identified. The Swedish universities Scales of Personality (SSP), a self-rating questionnaire, was used for evaluation of personality traits. High scores of personality traits related to neuroticism were associated with mood and/or anxiety disorders among both women and men. Another objective was to explore the experience of childlessness three years after unsuccessful IVF by a qualitative-approach, assessing data by interviews. Failure after IVF was experienced by women in terms of grief, whereas men took upon themselves a supportive role not expressing grief. A need for professional support and counselling in how to handle grief was described. An unstructured end after IVF treatment left unanswered questions. Three years after the end of treatment, men and women were still processing and had not adapted to childlessness, indicating the grieving process was unresolved.

Hysterektomi är ett kirurgiskt ingrepp där man opererar bort livmodern på kvinnor där en genital rubbning uppkommit. Syftet med detta arbete var att ge en klarare bild om hur kvinnor upplever detta ingrepp samt hur vårdpersonalen skall bemöta och kunna ge kvinnan stöd om så skulle behövas. Syftet med studien var att genom en litteraturstudie belysa kvinnors upplevelser av hysterektomi samt behov av stöd. En systematisk litteraturstudie gjordes där tretton vetenskapliga studier har inkluderats. Resultatet presenteras i två huvudkategorier, kvinnors upplevelser vid hysterektomi samt kvinnors behov av stöd. Båda kategorierna innefattade underkategorier vilka var livskvalitet, sexualitet, stöd samt information. Resultatet visade på att större delen av kvinnorna som genomgått hysterektomi var nöjda med ingreppet, då ett stort handikapp de dragits med en lång tid lättade eller försvann helt. Kvinnorna saknade information om tiden efter operationen. Information har en stor betydelse av hur kvinnorna upplever hysterektomi. Sammanfattningsvis är det viktigt att sjukvårdspersonal har den kunskapen att ge rätt information vid rätt tillfälle. För att hjälpa de kvinnor som skall genomgå hysterektomi bör vårdpersonalen även kunna vara ett stöd, så att sjukhusvistelsen blir en god upplevelse för dessa kvinnor.

The inspiration for the present studies was the learning concept that used professional patients (PP) as instructors for medical students in learning how to perfom the pelvic examination (PE). Interviews performed with women who were PPs showed that they experienced a continuous beneficial increase in knowledge. This promoted personal development related to bodily awareness and affirmed their femininity, making them less vulnerable and reversing their approach to their own body of being an object to becoming a subject. The growing ability to contribute to students’ learning and the feeling of being valuable enhanced the PPs self-esteem and well-being and promoted independence in the learning situation. Being a PP was rewarding and contributed to the feeling of being empowered and growing as a woman in the examination chair. Two models of teaching the PE to medical students were compared: with PPs or with clinical patients (CP). The outcome showed that the PP students were more skilful in palpating the terus and ovaries and performed more PEs during the clinical clerkship than did CP students. Female and male medical students were interviewed after they had performed their first PE with PPs as instructors. The female students’ most obvious concern was about looking and touching another women’s vulva whereas male students were concerned about how to establish rapport with the PP. The interactive and supportive feedback from the PPs enabled the students to overcome their hesitation and encouraged creative learning of interpersonal and palpation skills. The LS positively enhanced the female students’ awareness of own bodies and promoted a deeper interest in PEs, both as an examiner and as patients. The male students became aware of the importance of creating a beneficial interaction with the woman and gained an insight into a previously “unknown” female world that deepened their understanding of women’s possible vulnerability during a PE. Women at an outpatient clinic participated in individual LSs about the female anatomy and the PE, and performed a PE on a mannequin prior to visiting the gynaecologist. Following the visit interviews were performed to gain a deeper understanding of the impact of the LS. The womens’ active participation during the LS generated increased self-confidence and knowledge, triggered emowerment and promoted a creative ability to interact subsequently during their own PE. Part of the studies involved developing a questionnaire to measure the fear of performing the pelvic examination, the Fear of Pelvic Examination Scale (F-PEXS). The questionnaire was shown to have a very good reliability (e.g. Cronbach alpha is .96) and good construct validity. Engaging voluntary, healthy and knowledgeable women as instructors in the PE situation creates a safe and ethical learning environment and promotes interaction with students. Immediate constructive feedback enables students to integrate communication and behavioural skills in a professional manner whilst learning to palpate the uterus, facilitating an inner security as a future examiner. The learning sessions were of benefit to the PPs, the female students in the PP model, and the women in the clinical study. The acquired knowledge started something positive within the women; a will to act and find out more about themselves. The LSs initiated empowerment in the sense that an empowered person has increased capacity to act in goal-directed ways.

Background: Sex and stress steroids are metabolized to 3a-hydroxy-pregnane-steroid metabolites such as allopregnanolone (Allo) and tetrahydrodeoxycorticosterone (THDOC). Allo and THDOC are neuroactive steroids that are metabolized in the brain and act in brain as potent positive GABAA receptor function modulators. Allo as well as THDOC levels increase during stress. Allo has been associated with a number of symptoms and malfunctions such as impaired memory function and negative mood symptoms in a subgroup of individuals both for animals and humans. Pregnane steroids with 3b-hydroxy-configuration (3b-steroids) have been shown to reduce the Allo enhanced GABA effect. Aims: The aims for the present thesis were to investigate the effect of 3b-steroids on the GABA mediated GABAA receptor function in presence of positive GABAA receptor modulators. Further, the regional variances between the 3b-steroids as well as the mechanism of the effect were studied. Finally, the effect of stress steroid metabolites on the GABAA receptor function was investigated. Results: 3b-OH-5a-pregnane-20-one reduced the Allo enhanced GABA mediated chloride ion uptake into cortical microsacs. The 3b-isomer reduced the efficacy of Allo without shift the concentration response curve. It is therefore suggested that the 3b-isomer has a non-competitive effect. Further, it was shown that the 3b-isomer reduced the Allo effect in a selective way since the 3b-isomer did not interact with other positive modulators or with GABA itself. Five tested 3b-steroids reduced the Allo enhanced GABA mediated chloride ion uptake in cerebral cortex and hippocampus as well as the Allo prolongation on spontaneous inhibitory postsynaptic currents (sIPSCs) in preoptic nucleus. In cerebellum on the other hand the 3b-steroids showed to have weaker or no effect compared to the other tested regions. Interestingly, in absence of Allo, two of the 3b-steroids positively modulated the GABA stimulated GABAA receptor function. In absence of Allo, 5b-pregnane-3b,20(R)-diol increased the desensitization rate of current response. In contrast to the reducing effect on the Allo induced prolongation on sIPSCs, the effect of the 3b-steroid on GABA application, was not altered in presence of Allo. The mechanism of the 3b-steroid is therefore suggested being desensitization dependent in contrast to Allo, which has been suggested to decrease the GABA unbinding rate. In contrast to the enhanced effect of Allo, glucocorticoid metabolites reduced the GABA mediated chloride ion uptake in a concentration dependent way. The results in present thesis indicate that both sex and stress steroid metabolites interact with the GABAA receptor function. The knowledge that diversity of endogenous steroids interact with the GABAA receptor function is of importance for further understanding of different sex and stress steroid related symptoms and syndromes.

Bakgrund: Sexualitet hos äldre är precis som hos yngre en viktig del av livskvaliteten. Den sexuella förmågan och de sexuella behoven fortsätter långt upp i åren. Ett aktivt sexualliv har visat sig vara bra för välbefinnandet. Syfte: Syftet var att undersöka vilka faktorer som har en positiv påverkan på äldre kvinnors sexuella välbefinnande. Metod: En kvantitativ metod har används på ett redan insamlat datamaterial. Detta material består av omfattande enkäter som samlades in under åren 2000-2003. Huvudvariabel sexuellt välbefinnande har testats mot flera relevanta variabler. Analysmetoderna som användes var Chi-square test, univariat analys och slutligen en multivariat analys. Vi har valt att titta på den positiva odds kvoten, det vill säga vad som påverkar det sexuella välbefinnandet positivt. Resultat: Av den undersökta populationen skattade 25 % av kvinnorna att de hade ett bra sexuellt välbefinnande. Studien visade ett starkt samband mellan att känna sig uppskattad i hemmet och att vara nöjd med sitt sexuella välbefinnande. Att vara nöjd med sin kropp var en positiv faktor för det sexuella välbefinnandet. Signifikans fanns också för att ha ett bra humör, att vara icke rökare och att inte ha passerat menopaus. / Background: Sexuality among older persons are just as important to quality of life as it is to younger people. The sexual ability and sexual needs will continue up in years. An active sex life is good for the sexual satisfaction. Objective: The objective was to examine factors that have a positive impact on older women's sexual satisfaction. Method: A quantitative method was used on already collected material, consisting of extensive surveys collected during the years of 2000-2003. The main variable sexual satisfaction has been tested against several relevant variables. The analytical methods used were chi-square test, univariate analysis and finally a multivariate analysis. We chose to examine the positive odds ratio, (POR), that affects the sexual satisfaction positively. Results: Among the respondents 25% estimated that they had very good sexual satisfaction. The results indicates to be appreciated at home and happy with ones own body affected the sexual satisfaction positively. Having a good mood and not have passed menopause also have a positive affect of the older womens sexual satisfaction.

Thesis (M.D.)-University of Natal, Durban, 1979.

Background: Multiple factors contribute to mother-to-child transmission (MTCT) of HIV-1, including virological, obstetric and biological factors. Other possible contributory determinants for high MTCT rates include immunological factors such as host genetics and viral genetic variations. Despite several therapeutic, prophylactic and obstetric interventions to reduce the proportion of infants infected during labour and delivery, mechanisms for intrapartum HIV-1 transmission remain elusive and current interventions, could, therefore remain sub-optimal. Much controversy has surrounded the correlation of HIV-1 RNA (viral load) in the systemic and genital compartments of women. The influence of short-term antiretroviral (ARV) drugs on genital tract HIV-1 is also unclear. At the time the present study was initiated, a regimen of maternal intrapartum and neonatal postpartum single-dose Nevirapine (sdNVP) was the standard of care for the prevention of mother-to-child transmission (PMTCT). In most low and middle-income countries, including South Africa, sdNVP has been documented as effective intrapartum HIV-1 prevention based on plasma pharmacokinetic levels, decreased viral loads (HIV-1 RNA) and reduced rates of intrapartum transmission, yet operational studies continue to report high intrapartum transmission rates despite the administration of sdNVP. As a result perinatal HIV-1 transmission remains a significant public health concern in several African countries. Aim: The primary aim of this study was to describe the pharmacological dynamics of Nevirapine in association with virological and immunological risk factors for intrapartum HIV-1 transmission in a South African PMTCT programme where sdNVP was the standard of care. Methods: Following regulatory approval from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (UKZN), one hundred and twenty pregnant HIV-infected women who received the sdNVP regimen for prevention of mother-to-child HIV-1 transmission were enrolled between April-December 2006 at King Edward VIII Hospital (KEH) in Durban. Blood and cervicovaginal lavage (CVL) samples were collected from women at pre-NVP (during pregnancy) and post-NVP dosing (during labour/delivery). In addition to infant blood sampling at birth (post-NVP), postnatal infants were assessed at four and six weeks postnatally. Pharmacological laboratory investigations involved measurement of NVP drug concentration by Tandem Mass spectrophotometry. Virological investigations comprised HIV-1 RNA (viral load) quantitation, HIV-1 drug resistance testing (HIV-1 transmitting women only) and HIV-1 DNA PCR testing (infants only). Immunological investigations were only undertaken in a selected case-control subset of HIV-1 transmitting women and their infants. In this component, laboratory investigations included the determination of CCL3 and CCL3-L1 gene copy numbers, identification of single nucleotide polymorphisms (SNP’s) and haplotype characterisation of the CCL3 gene. All women were also screened for the presence of sexually transmitted infections (STI’s) during pregnancy. Results: One hundred and twenty women were enrolled onto this study. Of these, 110 women delivered 117 live infants (103 singletons and 7 twin pairs). Twelve (10.9%) women transmitted HIV-1 to their infants, while 95 (86.0%) were classified as non-transmitters. As a result of seven twin deliveries, the infant cohort comprised of 117 infants in total. Following two separate DNA PCR tests, HIV-1 infection was identified in 14 (11.9%) of study infants while the remaining 90 (76.9%) were exposed-uninfected. HIV infection status remained unknown for 13 infants due to infant demise (1.7%), lost to follow-up (7.7%) or study withdrawal (1.7%). During active labour (sampling that was best representative of the intrapartum phase) and within 20 hours of dosing, the median NVP concentration of 1070 ng/ml in the maternal systemic compartment was almost 44 times higher than the NVP levels detected in the genital compartment [24.5 ng/ml] (p < 0.001). NVP drug levels were below the 100 ng/ml therapeutic target in seven (13.7%) of 51 plasma and in all 39 CVL samples. While no significant association was found between NVP concentration in the systemic compartment and HIV-1 transmission (p = 0.4), this association was statistically significant in the genital compartment(p = 0.02). The median plasma NVP level detected among infants at birth was 83 times above the IC50 WT (10 ng/ml) and eight times higher than the 100 ng/ml therapeutic target for NVP. More than 71.0% of the infants achieved NVP drug levels above the therapeutic target. In general, higher levels of HIV-1 RNA (viral load) were observed in maternal plasma when compared to CVL. Following intrapartum sdNVP dosing, reduction in HIV-1 RNA levels did occur, however R80.0% of the women experienced no change to their HIV-1 RNA levels in both systemic and genital compartments during active labour. These findings were further supported by the strong correlation observed when comparing pre and post-NVP HIV-1 RNA levels in both maternal systemic [r = 0.81, p < 0.0001] and genital compartments [r = 0.80, p < 0.0001] during active labour. HIV-1 transmitting women had significantly higher viral loads than their non-transmitting counterparts in systemic and genital compartments, before and after intrapartum sdNVP administration. In terms of perinatal transmission this observation was only statistically significant for plasma (p = 0.02) and not CVL (p = 0.7). Maternal viral load was inversely correlated with maternal CD4 cell counts in both systemic and genital compartments. Almost 40.0% of women in this study had at least one type of STI detected during pregnancy. Maternal STI’s were detected in four (66.6%) intrapartum transmitting women and in 38 (38.8%) of non-transmitting women. No significant association was observed between the presence of maternal STI’s and the risk for intrapartum MTCT (p = 0.2,RR: 2.90, 95% CI: 0.60-15.40). The presence of maternal STI’s was associated with higher median viral loads in both systemic and genital compartments of all women, independent of intrapartum HIV-1 transmission. Despite trial-like conditions and optimal sdNVP dosing, the overall MTCT rate in this exclusively formula-fed cohort was 11.9%, of which 50.0% were in utero and 50.0% were intrapartum HIV-1 transmissions. In utero and intrapartum MTCT rates were 5.9% and 5.9% respectively. Discussion/Conclusion: Detectable CVL HIV-1 RNA that correlated well with plasma HIV-1 RNA, in conjunction with sub-optimal NVP drug concentration in maternal CVL during active labour, suggests that intrapartum HIV-1 infected women continue to act as reservoirs for both vertical and horizontal HIV-1 transmission throughout the duration of pregnancy. These findings confirm that the role of sdNVP in PMTCT was primarily one of infant prophylaxis. This was further supported by relatively unchanged maternal HIV-1 RNA (viral load) during active labour, in both systemic and genital compartments. Early identification of women who need highly active antiretroviral therapy (HAART), and initiation of such therapy as early as possible during pregnancy, not only benefits maternal health but remains the best prophylaxis against mother-to-child HIV-1 transmission. Universal access to HAART and improving strategies to optimize coverage of the current dual ARV regimen sdNVP and Zidovudine for PMTCT remain urgent research priorities in several resource-limited settings. Ongoing STI counseling, intensive screening/testing of women and their partners together promotion of condom usage, safer sex practices and aggressive STI treatment are simple interventions with tremendous impact for PMTCT in resource-limited settings. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.

Obstetric trauma is a major cause of faecal incontinence in women resulting in considerable social disability. Until recently the development of faecal incontinence has been attributed largely to damage to the pelvic nerves. However the advent of anal endosonography has added a new dimension to our understanding of the pathophysiology of faecal incontinence. In this thesis, gross dissection and histological studies of 19 anorectal specimens was performed to demonstrate the normal anatomy. Simultaneous dissection and sonography of the anorectum (14 in vivo and 12 in vitro studies) has clarified the normal sonographic anatomy of the anal sphincters. Anal endosonography was performed in 114 healthy volunteers to demonstrate gender differences in anal sphincter anatomy. A prospective study of 12 patients undergoing secondary sphincter repair and 15 patients undergoing lateral internal anal sphincterotomy has validated the appearance of sonographic sphincter defects. A new technique of demonstrating the anal sphincters at rest using vaginal endosonography has been demonstrated in 20 women. A prospective study of 202 pregnant women using anal endosonography and neurophysiological tests has demonstrated that 35% of primigravidae (13% symptomatic) and 44% of multigravidae (23% symptomatic) develop occult anal sphincter defects during vaginal delivery. Although pudendal nerve damage can be identified in 16% of women 6 weeks after delivery, in the majority this recovers with time. Forceps delivery was identified as the single independent variable associated with sphincter damage although damage was also sustained in the absence of instrumental delivery. In a separate study of 50 women who sustained a recognized third degree tear 47% were found to be symptomatic despite a primary sphincter repair. In 85% of these women persistent anal sphincter defects were identified sonographically. In a further study of 43 women who had an instrumental delivery (17 vacuum and 26 forceps) anal sphincter defects were identified in 81% (38% symptomatic) of women who were delivered by forceps compared to 12% (21% symptomatic) delivered by the vacuum extractor. One hundred and fifty doctors and midwives were interviewed to assess their knowledge and training in perineal anatomy and repair. There was a clear deficiency in knowledge and inconsistencies in classification of third degree tears were apparent highlighting the need for more focused training in perineal anatomy and repair. / Thesis (Ph.D.)-University of Natal, 1994.