Background: Irritable bowel syndrome (IBS) is an extremely common condition affecting approximately 10-15% of the population. Lower abdominal pain is a common feature and, if the patient also has gynaecological symptoms such as heavy periods, they may be referred to a gynaecologist especially when the bowel symptoms are relatively mild. In this setting a laparoscopy is often undertaken and endometriosis commonly identified as this condition affects up to 10% of women. Consequently pain is frequently attributed to the endometriosis even when it is relatively mild. However it is a common observation amongst gynaecologists that women with mild endometriosis often have severe symptoms which do not seem to respond well to treatment. This raises the possibility that their pain may not actually be due to endometriosis or is being amplified by the visceral hypersensitivity which is a characteristic feature of irritable bowel syndrome.Methods: 20 patients with minimal-mild endometriosis, 20 with moderate-severe endometriosis, 20 healthy volunteers (HV) who have had laparoscopy for sterilisation, 20 IBS patients and 20 patients with pain who were found to have a normal pelvis (on laparoscopy) were studied. Gastrointestinal, gynaecological, and noncolonic symptoms were recorded as well as demography, quality of life and psychological status. Visceral sensitivity was assessed in all patients and abdominal distension was studied in a sub group of 26 endometriosis patients and 20 IBS patients.Results: 20 (100%) of IBS patients, 13 (65%) of minimal-mild endometriosis patients, 11 (55%) of moderate-severe endometriosis patients, 17 (85%) of laparoscopic negative pain patients and no healthy volunteers fulfilled ROME III criteria for IBS. Patients with endometriosis and IBS had similar levels of visceral sensitivity which were significantly lower than that observed in controls (p=0·002, p<0·001).In particular, both minimal-mild and moderate-severe endometriosis patients had significantly lower (mean-95% CI) pain thresholds in mmHg 28.1(24.5, 31.6) and 28.8(24.9, 32.6) respectively compared with controls 39·5 (36·0, 43·0) p=0.001and p=0.002. However, with few exceptions, there were no distinguishing features between patients in terms of demography, symptomatology and distension.Conclusion: Clinically, it is very difficult to distinguish between endometriosis and IBS. However, visceral hypersensitivity appears to be a major component of endometriosis and may explain the problem of excessive pain especially in patients with mild disease offering a potential new target for treatment

<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.