Background: The objective of this thesis was to measure oxidative stress (OS) in women with Bipolar Disorder (BD) who used combined oral contraceptives (OCU). Based on our literature review, it was predicted that OCU would increase OS levels relative to non-contraceptive users (NCU) in women. Methods: Thirty-five participants (BD n=25; Control n=10) were recruited from an ongoing study based in British Columbia ‘The Systematic Treatment Optimization Program in Early Mania.’ Participants were administered psychological screening tools (Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale, Mini International Neuropsychiatric Interview and Hamilton Depression Rating Scale) and provided a blood sample for the assays (Lipid Hydroperoxide (LPH), Protein Carbonylation, 4-Hydroxynonenal, 3-Nitrotyrosine (3-NT) and 17-Beta Estradiol). Results: In our primary analysis we did not find differences in OS between BD and controls relative to OCU. Within our remaining analyses, only BD women (n=17) and who gave smoking status were included. We found 3-NT to be increased in OCU compared to NCU (F (1, 12) = 5.639, p = 0.035). With respect to mood stabilizer use, 3-NT was increased in OCU relative to NCU (F (1, 10) = 6.33, p=0.031). As for atypical antipsychotics, 3-NT was heightened in OCU adjunctive users compared to NCU who did not use atypical antipsychotics (F (3, 10) = 4.822, p = 0.025). As for our correlation analyses, YRMS correlated with 3-NT and LPH in OCU BD women (r(11)= 0.711, p=0.014 and r(11) = 0.676, p=0.022, respectively) and 17-Beta Estradiol correlated with LPH (r(17) = 0.598, p = 0.001). Our results are preliminary and are limited by our small sample size and various other factors (i.e. controls). Conclusion: The association between hormones and oxidative stress still remains controversial. Here we showed, after controlling for smoking, BMI and age the use of a COC significantly increased 3-NT in women with BD. Moreover, hormones may influence the relationship between OS and mood episodes. / Thesis / Master of Science (MSc)

Magister Pharmaceuticae - MPharm / Background: The effectiveness of the combined oral contraceptive pill as a family planning method is dependent on its quality. The quality of medicines on the healthcare market is established through postmarket quality studies. Methods: The quality of the combined oral contraceptive pill was established through the collection of samples from 17 (62%) private retail pharmacies in the Nyeri town of Kenya. Their quality was then determined through the assay of content of levonorgestrel and ethinylestradiol and the levonorgestrel dissolution test at the National Quality Control Laboratory. Findings: 13 of the 17 pharmacies were licensed with the Pharmacy and Poisons Board while 4 were unlicensed. Femiplan® was available in all the 17 pharmacies while Microgynon® was available in only 4 pharmacies. 17 samples of Femiplan® and 4 samples of Microgynon® were collected. None of the samples was counterfeit or falsely labeled. All the samples passed the assay of content of levonorgestrel and ethinylestradiol and the levonorgestrel dissolution test. Conclusion: Notwithstanding the fact this study provides a snapshot in time, it is reasonable to conclude that the combined oral contraceptive pill (0.15mg levonorgestrel and 0.03mg ethinylestradiol) in the Nyeri town of Kenya private retail pharmacies is of the right quality with respect to the quality tests of assay of content of levonorgestrel and ethinylestradiol and the levonorgestrel dissolution test.

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.