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.

Class of 2005 Abstract / Objectives: Describe the prevalence of alcohol and tobacco use in college women who use emergency contraception (EC) or oral contraceptives. Methods: This study was a descriptive, retrospective study that utilized patient charts to obtain clinical data including emergency contraception utilization, hormonal contraception utilization, alcohol and tobacco use. The primary dependent variables were smoking status and alcohol use. The overall prevalence of alcohol and tobacco use was calculated by counting the total number and percentage for each substance. Determining if descriptive variables vary according to type of contraception, groups were compared using a t-test for independent groups and a Chi square, respectively. The a priori alpha level is 0.05. Results: The most important finding in this study is students that obtained EC reported drinking alcohol at a significantly higher level than students who used hormonal contraception. 49% of students who used EC reported drinking 5 or more drinks a week. The data for the alcohol use was the only data that was found to be statistically significant (p<0.05). In this study 22% of students who requested EC had unprotected sex. A positive result seen in this study was that only 2% of the EC students requested EC more than once in the spring semester. Freshman composed 54% of the students that used EC during this study. Other data that was of interest was that 33% of students that used EC were currently using oral contraception but only 25% claimed that oral contraception incompliance was the reason for EC utilization. Implications: Prevalence of alcohol use is significantly higher in students who use EC than students who used hormonal contraception. This leads to the conclusion that students that use alcohol are more likely to engage in unprotected sex and therefore request EC. This study also has shown that nurses and physicians need to get more accurate information from students regarding tobacco and alcohol use.

Burundi’s high maternal and child mortality is caused in part by the high fertility rate, prompted by low rate of contraceptive use. Available sources report a contraceptive use of 18% among married women, but this excludes unmarried sexually active women. This study employed mixed methods to understand rates of contraceptive use in rural Burundi. We first assessed availability and uptake of contraceptives in 39 health clinics in the rural districts of Rumonge and Bururi. We selected sites with different utilization rates and conducted individual interviews and focus group discussions. 56 individuals participated including women, men, facility managers and community leaders. Uptake of family planning averaged 2.96%. Greater uptake was positively associated with the number of health professionals engaged and trained in family planning service provision as well as the number of different types of contraceptives available. Uptake was inversely associated with duration of stockouts and number of contraceptives stocked out. Qualitative data pointed to scarce resources, sociocultural factors, fear of disclosure and side effects, partner’s disapproval, and lack of information on modern contraceptives as explanations of low uptake. Interventions would need to take into account one or more of these factors in order to improve uptake of family planning

Teenage pregnancy rates in the U.S. are among the highest in the world for industrialized countries. The generally accepted reason is not that American teenagers are more sexually active but that they contracept less than do teenagers in other industrialized countries. This dissertation reports on a study that was undertaken for two purposes. One purpose was to develop and test two models of contraceptive choice among American teenagers: a "likelihood-of-use" model to predict the likelihood of sexually active teenagers' using contraception, and a "medical-or-nonmedical" model to predict whether teenagers who use contraception are likely to use medical or nonmedical methods. The second purpose was to explore the level of support for the two models among black and white teenagers separately. The theoretical underpinning of the models is value-expectancy theory. The models' exogenous variables are based on the prevailing strategy for preventing teenage pregnancy among American teenagers, a strategy initially advocated by Joy G. Dryfoos. The strategy involves the use of access-to-contraception programs, educational programs, and life options programs. The data used in the study were on 449 subjects drawn from the 1979 National Survey of Young Women, a probability-sample survey of women in the U.S. aged 15-19. The subjects were those survey respondents who were black or white, sexually active, never married, and never pregnant. The statistical technique used in the study was logistic regression. Test results supported three of four hypotheses constituting the medical-or-nonmedical model and two of seven hypotheses constituting the likelihood-of-use model. The results for each model offered support for using two of the three programs constituting the prevailing pregnancy-prevention strategy: access-to-contraception programs and educational programs. Exploration of the level of support for each of the two models among black and white teenagers indicated that support for each model differed between the two groups of teenagers.

Philosophiae Doctor - PhD / Access to life-saving commodities and related services for women and children is a fundamental component of universal health coverage. However, countries confront numerous intractable challenges, such as aligning regulatory practices, enhancing health workforce capacity, and effectively managing supply chains, to ensure essential reproductive, maternal, newborn and child health (RMNCH) commodities and services reach all communities. To address these entrenched obstacles, the UN Commission on Life Saving Commodities for Women and Children (UNCoLSC) in 2012 outlined a series of recommendations to improve access to 13 low-cost and high-impact commodities. This thesis explores the improvements and remaining barriers to accessing life-saving commodities for women and children in sub-Saharan Africa and Southeast Asia. In addition, this thesis showcases how effective data-informed decision-making can support prioritized RMNCH investments and equitycentered action.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, cardiogenic shock, and sudden cardiac death in women of reproductive age who have no traditional risk factors for coronary artery disease. The etiology, prognosis, and treatment of SCAD remain poorly defined. Coronary angiography is the gold standard for diagnosis. Management includes medical therapy and revascularization procedures using percutaneous intervention and coronary artery bypass grafting. Possible mechanisms of SCAD include rupture of atherosclerotic plaque or vasa vasorum, hemorrhage between the outer media and external lamina with intramedial hematoma expansion, and compression of the vessel lumen. We report a case of SCAD in a 39-year-old woman presenting with ST-elevation myocardial infarction midway through her menstrual cycle. Her medications included fenfluramine for obesity and hydrochlorothiazide, amlodipine, and atenolol for hypertension.

Although women constitute more than half of the estimated 34-40 million people living with HIV/AIDS worldwide, little is known about the early events of HIV-1 infection in the female genital tract (FGT). Genital epithelial cells (GECs) line the FGT and act as intrinsic barriers providing mechanical protection against foreign microbes. GECs are also sentient and are capable of sensing and immunologically responding to various types of pathogens including sexually transmitted infections (STIs). These responses play a central role in preventing disease and also help mobilize both innate and adaptive immune cells against invading threats. While it is well understood that GECs exert important physical and immunological protective roles in the FGT, little is known regarding the role of GECs and GEC inflammatory responses in HIV infection. It is estimated that 40% of all new HIV infections are established each year in the FGT. Our understanding of the early events following HIV transmission in the FGT remains particularly elusive in the context of endogenous or exogenous factors found in the genital microenvironment that may influence susceptibility to HIV-1. Inflammation is known to play a critical role in increasing HIV susceptibility, replication as well as initiating and maintaining chronic immune activation, a hallmark of disease progression. Among the key factors in the FGT that are known to or that could influence inflammation are sexually transmitted co-infections and female sex hormones. The work summarized in this thesis examines how GEC innate immune responses to co-infecting microbes or female sex hormones impact HIV infection and replication in the FGT. Our results show that GEC innate immune response against herpes simplex virus type 2 (HSV-2), a common HIV co-infecting agent, consists of elevated proinflammatory cytokines and chemokines in addition to biologically active interferon-β. Furthermore, our results show that these responses require potent viral HSV-2 replication and that proinflammatory cytokine and chemokine responses are enhanced in the absence of the HSV-2 virus host shutoff protein. Based on this work, we decided to investigate whether GEC inflammatory responses to common STIs played a role in regulating HIV replication in T-cells. We found that HIV co-infecting microbes, specifically HSV-1, HSV-2 and Neisseria gonorrhoeae, directly induced HIV replication in T-cells, and caused primary GECs to upregulate inflammatory responses that indirectly increased HIV replication in T-cells. Next we examined a translational aspect of the aforementioned studies by examining whether blocking inflammatory pathways, using the broad anti-inflammatory compound curcumin, could provide prophylactic or therapeutic protection against HIV. We found that curcumin pre-treatment a) protected the genital epithelial barrier against HIV-1-mediated disruption and inflammation, b) prevented the gp120-mediated upregulation of chemokines by GECs that recruit HIV target cells to the FGT, c) blocked GEC innate inflammatory responses to co-infecting microbes and indirect activation of the HIV promoter in T-cells, d) decreased HIV amplification in chronically infected T-cells and e) blocked HSV-2 viral replication in GECs by a mechanism that likely involves NFκB. Lastly, it has long been speculated that female sex hormones can regulate inflammatory responses, and numerous lines of evidence suggest that they may also regulate susceptibility to HIV-1. Thus, we investigated how female sex hormones and the hormonal contraceptive medroxyprogesterone acetate (MPA), used by more than 100 million women worldwide, regulated HIV infection and replication in GECs and whether inflammation played an important role in this regulation. Our results showed that progesterone and in particular MPA increased uptake of HIV-1 and transcytosis, but not replication, across GECs – in the absence of a proinflammatory milieu - and that this enhanced transcytosis resulted in increased infection of HIV target cells. These results demonstrate that sex hormones and co-infection both play an important role in regulating HIV-1 infection and replication in the FGT. Furthermore, our results suggest that anti-inflammatory compounds such as curcumin may offer paradigm shifting prophylactic or therapeutic strategies against HIV-1 infection and future research should investigate its potential benefit in vivo. / Thesis / Doctor of Philosophy (Medical Science)

Acne vulgaris is an extremely common disease, affecting large numbers of adolescents and adults, with substantial physical and psychosocial impacts. Antibiotics have been used for many years in the anti-microbial and anti-inflammatory treatment of acne, and have generated reasonable success rates. In recent years, along with a growing popularity of oral contraceptives to reduce unwanted pregnancies, they have also been applied in acne treatment because of their overall anti-androgenic effects. Very little direct comparisons between these two methods have been published, and this study serves as a preliminary measure for the effectiveness of both treatments against each other. Using an extensive literature search of PUBMED and MEDLINE for randomized clinical trials involving antibiotics or oral contraceptives, data were taken and used in an analysis to assess efficiency of both drug groups in the reduction of lesion counts and percentage reduction in inflammatory acne lesions, non-inflammatory lesions, and total lesions based off original baseline counts in each study. A total of 15 studies were used in the analysis. Antibiotics, oral contraceptives, and placebo treatment groups were evaluated at three months’ time, while oral contraceptives and placebo treatments were also continued out to six months to reflect longer trial durations. In all cases, antibiotics were superior to placebo at three months. Oral contraceptives were also superior to all placebo arms at both three and six months, except for in the average percent reduction of total lesions where the placebo at six months is not significantly different than the contraceptives at three months. Antibiotics and contraceptives showed no significant difference between each other at three or six months times, except for the lesion number reduction at three months for inflammatory lesions compared to antibiotics. All comparisons used the average percentage or number reduction, and 95% confidence intervals to determine significance. After three months, antibiotics showed a 45.40% weighted mean reduction in total lesion counts, compared to 36.41% for oral contraceptives at three months and 43.76% at six months. With the confidence intervals, the ranges for significance are 38.40%-52.40%, 31.92%-40.90%, and 33.87%-53.64% respectively, corresponding to an insignificant difference between all three treatments. Percentage changes for both inflammatory and non-inflammatory lesion reductions were also similar in their confidence intervals overlapping. The study showed a surprising similarity between antibiotics and contraceptives in their ability to treat acne, in both inflammatory and non-inflammatory lesions. With the exception of the three month antibiotics out-performing the oral contraceptives at three months’ time for reduction of inflammatory lesions, the percentage reduction was not significantly different, indicating discrepancies with starting numbers. Overall, both treatments were effective in the treatment of acne lesions, but the limitations of oral contraceptives including their utility is confined to women, and the relatively short recommended treatment time for oral antibiotics each have their drawbacks. Oral contraceptives seem to represent a better long term treatment plan for women who are comfortable taking birth control.

Background: HSV-2 was estimated to infect 491 million people worldwide, with women disproportionately affected by HSV-2. Understanding factors that influence susceptibility to HSV-2 in women is important in preventing infections. Through various studies, the progestin-based contraceptive DMPA exhibited immunosuppressive effects, and has shown increased susceptibility to HIV and HSV-2. Studies comparing DMPA to other contraceptives like NET suggest that NET may be safer. In vivo NET effects have not been characterized thoroughly to better understand the effect of NET on susceptibility to HSV-2. Therefore, this study aimed to compare the effects of NET and DMPA in mouse models that affect susceptibility to HSV-2. We hypothesized that NET treated mice will have decreased susceptibility to HSV-2 compared to DMPA but elevated compared to normal mice. Method of study: Ovariectomized mice were treated with DMPA (2mg) and NET (2 mg injections, 2.5 mg pellets or 5 mg pellets) for 10 days and intravaginally immunized with HSV-2 TK-, then intravaginally challenged with WT HSV-2 ~4-7 weeks later. Primary intravaginal WT HSV-2 challenges were conducted in ovariectomized and normal mice after 10 days of DMPA and NET treatment. Viral titers, pathology and survival were examined. Mucus production in the vagina was investigated through immunohistology. Effects of hormones on immune cells were explored in the lymph nodes, spleens, and vaginal tracts through flow cytometry. Results: Increased mucus was consistently observed in the vaginal tracts of mice after treatment with NET 2.5 mg and 5 mg treated mice, but not with DMPA Therefore, NET treated mice displayed reduced viral shedding and delayed pathology compared to DMPA treated mice. No significant changes occurred in immune cells analyzed post DMPA and NET treatment, although there were trends of increased T cells in progestin treated mice. However, more experiments need to be conducted to confirm observed trends. Conclusion: NET treatment in mice results in mucus production in the vaginal tract, a potential mechanism impeding intravaginal HSV-2 infection and could be applied to other STIs. This provides insight into protective effects of NET compared to DMPA allowing women to make informed decisions regarding hormonal contraceptives. / Thesis / Master of Science in Medical Sciences (MSMS)

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