abstract: This is a project about medicine and the history of a condition called premenstrual syndrome (PMS), its “discovery” and conceptual development at both scientific and socio-cultural levels. Since it was first mentioned in medical literature, PMS has been explored empirically as a medical condition and conceptually as non-somatic cultural phenomenon. Many attempts have been made to produce scientific, empirical evidence to bolster the theory of PMS as a biological disease. Some non-medical perspectives argue that invoking biology as the cause of PMS medicalizes a natural function of the female reproductive system and shallowly interrogates what is actually a complex bio-psycho-social phenomenon. This thesis questions both sides of this debate in order to reveal how criteria for PMS were categorized despite disagreement surrounding its etiology. This thesis illustrates how the concept of PMS developed and was informed by the discovery of hormones and the resulting field of endocrinology that provided a framework for conceptualizing PMS. It displays how the development of the medical diagnostic category of PMS developed in tandem with the emergence of the field of endocrinology and was legitimized and effectively medicalized through this connection. The diagnosis of PMS became established though the diagnostic techniques like questionnaires in spite of persistent disagreement over its definition. The thesis shows how these medical concepts and practices legitimated the category of PMS, and how it has become ubiquitous in contemporary culture. / Dissertation/Thesis / Masters Thesis Biology 2016

Ett grafiskt designprojekt, en booklet med fokus på PMS och PMDS. Innehållet i bookleten är objektivt och subjektivt i form av information samt visualiseringar. Personer med PMS eller PMDS har kommit till uttryck genom sina berättelser och självporträtt. / A graphic design project, a booklet that focuses on PMS and PMDD. The content of the booklet is objective and subjective with information and visualizations. Persons with PMS or PMDD has manifested through their stories and self-portraits.

Introdução: O diagnóstico da Síndrome Pré-menstrual (SPM) é um desafio. O uso de questionários estruturados está bem estabelecido, e a ferramenta mais aceita é o DRSP, um questionário prospectivo auto preenchido por ao menos dois meses. O PSST é um questionário retrospectivo de autoaplicação, preenchido em um único momento. Objetivo: comparar estes dois instrumentos (PSST e DRSP) para o diagnóstico da SPM. Método: Um estudo transversal com 127 mulheres entre 20 a 45 anos com queixas de SPM. As mulheres foram avaliadas quanto ao peso, altura, Índice de Massa Corporal (IMC). Após exclusão de casos de depressão através do Prime-MD, as pacientes completaram o PSST e foram orientadas a preencherem o DRSP durante dois meses. A concordância entre os dois questionários foi avaliado pelo cálculo de Kappa (k) e valores do coeficiente PABAK. Resultados: Do total de mulheres que atenderam ao chamado, 282 (74%) preencheram os critérios de elegibilidade e responderam o PSST. Entre estas 282 mulheres, somente 127 (45%) completaram o questionário diário (DRSP) por dois ciclos. O percentual das mulheres com diagnóstico de SPM através do DRSP foi de 74,8%, e pelo PSST foi 41,7%. O percentual das mulheres com diagnóstico de TDPM pelo DRSP foi de 3,9%, e pelo PSST foi de 34,6%. Assim, verificou-se uma maior prevalência de SPM com o DRSP do que com o PSST. De outra parte a TDPM foi mais dignosticada pelo PSST do que com o DRSP. O número de pacientes consideradas “normais” foi semelhante com os dois instrumentos. Na avaliação entre os dois instrumentos verificou-se não haver nenhuma concordância (Kappa = 0,12) nos resultados do diagnóstico de SPM e TDPM (Coeficiente Pabak resultou = 0,39). Para a trigem de SPM/TDPM o PSST tem uma sensibilidade de 79% e especificidade de 33,3%. Conclusão: O PSST deve ser considerado como uma ferramenta de triagem diagnóstica. Conclui-se que os casos SPM/TDPM do PSST devem ser sempre melhor avaliados pelo DRSP. / Background: The diagnosis of Premenstrual Syndrome (PMS) is a challenge. The use of structured questionnaires is well established and the most accepted is the DRSP, a prospectively self-administered questionnaire that needs two months at least to be completed. The PSST is a retrospective self-scale questionnaire, filled at a single time. Aim: To compare these two instruments (PSST and DRSP) to diagnosis PMS. Methods: A cross-sectional study with 127 women between 20 and 45 years with PMS complaints. The women were evaluated about weight, high, Body Mass Index (BMI). After the exclusion of depression by the Prime-MD Questionnaire, the PSST was completed and the women were oriented to complete the DRSP for two months. The agreement between the two questionnaires was assessed by calculating the Kappa (k) and PABAK values. Results: 282 (74% of all the women) women met eligibility criteria and answered the PSST. Only 127 (45% of the 282 women) completed the daily questionnaire (DRSP) for two cycles. The percentual of women with PMS diagnosis by the DRSP was 74.8%, and by PSST was 41.7%. The percentual of women with PMDD diagnosis by the DRSP was 3.9%, and by the PSST was 34.6%. The number of patients considered “normal” (with the symptoms above the necessary for the diagnostic the PMS) was similar with both questionnaires. We found no agreement between the two instruments (Kappa = 0.12) in the diagnosis of PMS and PMDD (Pabak coefficient keep this result = 0.39). For screening PMS/PMDD the PSST has a sensitivity of 79% and a specificity 33.3%. Conclusion: The PSST should be considered as diagnostic screening tool. We concluded that positive PMD/PMDD cases of PSST should be ever better evaluated by DRSP.

Introdução: O diagnóstico da Síndrome Pré-menstrual (SPM) é um desafio. O uso de questionários estruturados está bem estabelecido, e a ferramenta mais aceita é o DRSP, um questionário prospectivo auto preenchido por ao menos dois meses. O PSST é um questionário retrospectivo de autoaplicação, preenchido em um único momento. Objetivo: comparar estes dois instrumentos (PSST e DRSP) para o diagnóstico da SPM. Método: Um estudo transversal com 127 mulheres entre 20 a 45 anos com queixas de SPM. As mulheres foram avaliadas quanto ao peso, altura, Índice de Massa Corporal (IMC). Após exclusão de casos de depressão através do Prime-MD, as pacientes completaram o PSST e foram orientadas a preencherem o DRSP durante dois meses. A concordância entre os dois questionários foi avaliado pelo cálculo de Kappa (k) e valores do coeficiente PABAK. Resultados: Do total de mulheres que atenderam ao chamado, 282 (74%) preencheram os critérios de elegibilidade e responderam o PSST. Entre estas 282 mulheres, somente 127 (45%) completaram o questionário diário (DRSP) por dois ciclos. O percentual das mulheres com diagnóstico de SPM através do DRSP foi de 74,8%, e pelo PSST foi 41,7%. O percentual das mulheres com diagnóstico de TDPM pelo DRSP foi de 3,9%, e pelo PSST foi de 34,6%. Assim, verificou-se uma maior prevalência de SPM com o DRSP do que com o PSST. De outra parte a TDPM foi mais dignosticada pelo PSST do que com o DRSP. O número de pacientes consideradas “normais” foi semelhante com os dois instrumentos. Na avaliação entre os dois instrumentos verificou-se não haver nenhuma concordância (Kappa = 0,12) nos resultados do diagnóstico de SPM e TDPM (Coeficiente Pabak resultou = 0,39). Para a trigem de SPM/TDPM o PSST tem uma sensibilidade de 79% e especificidade de 33,3%. Conclusão: O PSST deve ser considerado como uma ferramenta de triagem diagnóstica. Conclui-se que os casos SPM/TDPM do PSST devem ser sempre melhor avaliados pelo DRSP. / Background: The diagnosis of Premenstrual Syndrome (PMS) is a challenge. The use of structured questionnaires is well established and the most accepted is the DRSP, a prospectively self-administered questionnaire that needs two months at least to be completed. The PSST is a retrospective self-scale questionnaire, filled at a single time. Aim: To compare these two instruments (PSST and DRSP) to diagnosis PMS. Methods: A cross-sectional study with 127 women between 20 and 45 years with PMS complaints. The women were evaluated about weight, high, Body Mass Index (BMI). After the exclusion of depression by the Prime-MD Questionnaire, the PSST was completed and the women were oriented to complete the DRSP for two months. The agreement between the two questionnaires was assessed by calculating the Kappa (k) and PABAK values. Results: 282 (74% of all the women) women met eligibility criteria and answered the PSST. Only 127 (45% of the 282 women) completed the daily questionnaire (DRSP) for two cycles. The percentual of women with PMS diagnosis by the DRSP was 74.8%, and by PSST was 41.7%. The percentual of women with PMDD diagnosis by the DRSP was 3.9%, and by the PSST was 34.6%. The number of patients considered “normal” (with the symptoms above the necessary for the diagnostic the PMS) was similar with both questionnaires. We found no agreement between the two instruments (Kappa = 0.12) in the diagnosis of PMS and PMDD (Pabak coefficient keep this result = 0.39). For screening PMS/PMDD the PSST has a sensitivity of 79% and a specificity 33.3%. Conclusion: The PSST should be considered as diagnostic screening tool. We concluded that positive PMD/PMDD cases of PSST should be ever better evaluated by DRSP.

Introdução: O diagnóstico da Síndrome Pré-menstrual (SPM) é um desafio. O uso de questionários estruturados está bem estabelecido, e a ferramenta mais aceita é o DRSP, um questionário prospectivo auto preenchido por ao menos dois meses. O PSST é um questionário retrospectivo de autoaplicação, preenchido em um único momento. Objetivo: comparar estes dois instrumentos (PSST e DRSP) para o diagnóstico da SPM. Método: Um estudo transversal com 127 mulheres entre 20 a 45 anos com queixas de SPM. As mulheres foram avaliadas quanto ao peso, altura, Índice de Massa Corporal (IMC). Após exclusão de casos de depressão através do Prime-MD, as pacientes completaram o PSST e foram orientadas a preencherem o DRSP durante dois meses. A concordância entre os dois questionários foi avaliado pelo cálculo de Kappa (k) e valores do coeficiente PABAK. Resultados: Do total de mulheres que atenderam ao chamado, 282 (74%) preencheram os critérios de elegibilidade e responderam o PSST. Entre estas 282 mulheres, somente 127 (45%) completaram o questionário diário (DRSP) por dois ciclos. O percentual das mulheres com diagnóstico de SPM através do DRSP foi de 74,8%, e pelo PSST foi 41,7%. O percentual das mulheres com diagnóstico de TDPM pelo DRSP foi de 3,9%, e pelo PSST foi de 34,6%. Assim, verificou-se uma maior prevalência de SPM com o DRSP do que com o PSST. De outra parte a TDPM foi mais dignosticada pelo PSST do que com o DRSP. O número de pacientes consideradas “normais” foi semelhante com os dois instrumentos. Na avaliação entre os dois instrumentos verificou-se não haver nenhuma concordância (Kappa = 0,12) nos resultados do diagnóstico de SPM e TDPM (Coeficiente Pabak resultou = 0,39). Para a trigem de SPM/TDPM o PSST tem uma sensibilidade de 79% e especificidade de 33,3%. Conclusão: O PSST deve ser considerado como uma ferramenta de triagem diagnóstica. Conclui-se que os casos SPM/TDPM do PSST devem ser sempre melhor avaliados pelo DRSP. / Background: The diagnosis of Premenstrual Syndrome (PMS) is a challenge. The use of structured questionnaires is well established and the most accepted is the DRSP, a prospectively self-administered questionnaire that needs two months at least to be completed. The PSST is a retrospective self-scale questionnaire, filled at a single time. Aim: To compare these two instruments (PSST and DRSP) to diagnosis PMS. Methods: A cross-sectional study with 127 women between 20 and 45 years with PMS complaints. The women were evaluated about weight, high, Body Mass Index (BMI). After the exclusion of depression by the Prime-MD Questionnaire, the PSST was completed and the women were oriented to complete the DRSP for two months. The agreement between the two questionnaires was assessed by calculating the Kappa (k) and PABAK values. Results: 282 (74% of all the women) women met eligibility criteria and answered the PSST. Only 127 (45% of the 282 women) completed the daily questionnaire (DRSP) for two cycles. The percentual of women with PMS diagnosis by the DRSP was 74.8%, and by PSST was 41.7%. The percentual of women with PMDD diagnosis by the DRSP was 3.9%, and by the PSST was 34.6%. The number of patients considered “normal” (with the symptoms above the necessary for the diagnostic the PMS) was similar with both questionnaires. We found no agreement between the two instruments (Kappa = 0.12) in the diagnosis of PMS and PMDD (Pabak coefficient keep this result = 0.39). For screening PMS/PMDD the PSST has a sensitivity of 79% and a specificity 33.3%. Conclusion: The PSST should be considered as diagnostic screening tool. We concluded that positive PMD/PMDD cases of PSST should be ever better evaluated by DRSP.

Ungefär var 20:e kvinna i Sverige lider av svåra premenstruella besvär, varav flertalet upplever symtom som vid en medelsvår till svår depression (PMS-förbundet u.å, Wikman m.fl. 2022). Trots ett stort lidande för de som drabbas så råder det fortfarande okunskaper i samhället kring diagnosen och dess inverkan i människors liv. Könsspecifika tillstånd/sjukdomar där kvinnliga patienter är överrepresenterade, som vid PMDS har en tendens att bli underprioriterade i samhället (Annell 2016).  Syftet med den här studien var att undersöka och öka förståelsen för kvinnors upplevelser och erfarenheter av att leva med svåra premenstruella besvär och på så sätt även utveckla förståelser för hur det sociala arbetets praktik kan stödja och hjälpa kvinnor som lider av detta. Min utgångspunkt har varit induktiv och utforskande med fokus på kvinnans egna perspektiv, upplevelser och erfarenheter av att leva med PMDS/PMS (Kvale & Brinkmann 2014). För att svara till studiens syfte så har jag valt att använda mig av kvalitativa intervjuer. Jag har genomfört semistrukturerade intervjuer tillsammans med 9 kvinnor som lider av PMDS/svårare PMS. Det empiriska materialet har sedan tolkats utifrån narrativ psykologi och begreppen biografiskt avbrott och livsomställning.  Studiens resultat visar hur de premenstruella besvären har genomsyrat kvinnornas vardag och tillvaro och påtagligt påverkat livssituationen och begränsat viktiga livsområden. I studien framkommer hur det sociala livet och de nära relationerna har påverkats negativt och hur det emotionella måendet bidragit till tvivel och ifrågasättande av förmågor och färdigheter, resurser, roller, livsval och framtidsmöjligheter samt starka känslor av otillräcklighet, skuld och skam. Det emotionella måendet har också inverkat på studier och arbetsliv, så som svårigheter att avsluta studier, att ansöka om och behålla arbete, ökad sjukfrånvaro samt ökade svårigheter att genomföra arbetsuppgifter. Vidare visar studiens resultat hur PMDS/PMS blir en tyst erfarenhet i kvinnans liv. Att dölja sitt mående och aktuella situation samt uppleva farhågor kring att möta negativa attityder och oförstående begränsar och försvårar kvinnans livsvillkor. Andra försvårande omständigheter är upplevda okunskaper kring PMDS inom hälso- och sjukvården, den otillräckliga tillgången på fungerande behandling samt osynligheten och bristen på kunskap kring diagnosen i samhället. Studiens resultat visar vidare hur insikten, kunskapen och förståelsen kring det egna måendet, kroppen och den aktuella situationen har varit helt avgörande för att kunna må bättre, skapa en ökad förståelse kring sig själv och en hållbarare, meningsfullare tillvaro.  Studien visar vidare hur transparens och tydlighet kring upplevt mående och aktuell situation, samt att få dela upplevelser och erfarenheter tillsammans med andra är viktiga hjälpsamma aspekter i kvinnornas liv. Slutligen visar studiens resultat hur det sociala arbetets praktik kan ha en betydelsefull roll i att stödja och hjälpa kvinnor som lider av PMDS/PMS. Min förhoppning är att resultaten från denna studie kan bidra till inspiration och nya perspektiv för alla som på olika sätt arbetar med att främja kvinnors psykiska hälsa. / Approximately one in 20 women in Sweden experiences severe premenstrual issues with the majority displaying symptoms akin to moderate to severe depression ((PMS-förbundet u.å, Wikman m.fl. 2022). Despite the considerable distress faced by those suffered, societal understanding of the diagnosis and its impact remains limited. Conditions and diseases predominantly affecting women, such as PMDD, tend to receive inadequate attention (Annell 2016).  The aim of this study was to explore and enhance comprehension of women’s experiences of severe premenstrual disorder, and thereby advancing insights into how social work can assist and support those afflicted My approach was inductive and exploratory, focusing on women’s individual perspectives and experiences with PMDD/PMS (Kvale & Brinkman 2014). To fulfill the study’s purpose, I have chosen to use qualitative interviews. I conducted semi-structured interviews with 9 women experiencing PMDS and more severe PMS. The empirical data were then interpreted using narrative psychology and the theoretical concepts of biographical interruption and life adjustment.  The findings reveal how premenstrual issues permeate women’s daily lives, significantly impacting their life situations and constrain essential aspects. The study underscores negative effects on social life, close relationships, emotional state, self-doubt, abilities, roles, choices, and thoughts about the future. Feelings of inadequacy, guilt and shame are also prominent. The emotional state influences academic and professional pursuits. Additionally, the study highlights how PMDD/PMS remains a silent burden in women’s lives.  Increased awareness and knowledge about PMDD in society, accessible treatment options, and diagnosis prioritization can enhance women’s wellbeing and living conditions. The study emphasizes the importance of women’s personal comprehension of their medical condition. Transparency, clarity about mood, sharing experiences with other and social support are crucial factors in women’s lives. The study underscores social works significant role in aiding women dealing with PMDD/PMS.

Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors. Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids. Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA). Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior. Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats. / Stress- och könshormoners verkningar på centrala nervsystemet

Bakgrund: Premenstruell dysforisk störning (PMDS) är en allvarlig form av premenstruellt syndrom (PMS) som drabbar 3–8% av kvinnor i reproduktiv ålder. Emotionell dysreglering är kardinalsymptom för PMDS. Orsaken är ännu ej är helt klarlagd, men troligen råder hormonell överkänslighet i centrala nervsystemet. Identifikation, bemötande och omvårdnad från hälso- och sjukvårdspersonal är avgörande för bibehållen livskvalitet. Syfte: Syftet är att undersöka kvinnors upplevelser av premenstruell dysforisk störning. Metod: Litteraturöversikt med kvalitativ metod och induktiv ansats. Artikelsökningen gjordes i databaserna MEDLINE, CINAHL och PsycInfo. Tolv artiklar från år 2006–2022 inkluderades i resultatet. Fribergs dataanalysmodell användes. Resultat: I resultatet framkom två huvudteman; Begränsningar till följd av PMDS samt försök att hantera PMDS, vilka underbyggdes av sex subteman. Slutsats: Till följd av PMDS upplevdes sociala, känslomässiga, utbildnings- och yrkesmässiga begränsningar. Kvinnor försökte hantera livet med PMDS på olika sätt. Vikten av att såväl kvinnor själva som hälso- och sjukvårdspersonal besitter kunskap om PMDS var avgörande för att undvika onödigt lidande och försämrad livskvalité. / Background: Premenstrual Dysphoric Disorder (PMDD) is a severe type of Premenstrual Syndrome (PMS) affecting 3–8% of women at reproductive age. Emotional dysregulation is the primary symptom for PMDD. The cause is not yet entirely confirmed but probably it is due to hormonal oversensitivity in the central nervous system. Health professionals' identification, respond and nursing is crucial in order to substantiate women's perceived quality of life. Aim: The aim is to describe women’s experiences of premenstrual dysphoric disorder. Method: A literature review with qualitative method and inductive research approach. The result was based on twelve articles from year 2006-2022 which underwent examination according to templates from Friberg’s analysis model. Result: Two main themes were identified as Limitations due to PMDD and women’s ways of handling the life with PMDD. Those were supported by 6 sub-themes. Conclusion: Social, emotional, educational and work-related limitations due to PMDD were presented along with women´s different ways of trying to handle their life with PMDD. It was found highly important that both women themselves and health professionals have knowledge about PMDD in order to avoid unnecessary suffering and negatively affected quality of life.

<p>Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. </p><p>Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. </p><p>The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition.</p><p>The partial 5-HT_1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT₂ receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. </p><p>The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. </p><p>Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.</p>

Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition. The partial 5-HT1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT2 receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.