A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Research question: What is the difference in prevalence of LARCs between women living in urban and rural areas of Latin America and the Caribbean (LAC)? Background, significance, and rationale: While LARCs have been shown to be effective, approved for long duration of use, and cost-effective there is an unmet need for this type contraception in rural areas. The LAC region has a need for improved family planning services, evidenced by the high percentage of maternal deaths due to unsafe abortions. Methods: Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted between 2010 and 2015 in LAC countries were reviewed and analyzed to determine difference in prevalence of LARC use between women living in urban versus rural areas. Additionally, a systematic literature review was performed resulting in selection of 11 primary research articles evaluated for LARC prevalence and sociodemographic factors associated with LARC use.

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.

abstract: Oral contraceptives are one of the most frequently used forms of birth control among young women. However, research has shown that this type of medication can contribute to negative changes in mood and diminished vitamin status. In particular, women taking oral contraceptives are at an increased risk of vitamin B6 deficiency due to changes in enzyme activity with estrogen intake. Depressed mood is one of the known symptoms of vitamin B6 deficiency as this vitamin acts as an essential cofactor in converting tryptophan to the neurotransmitter, serotonin. Lack of adequate levels of vitamin B6 therefore contribute to decreased production of serotonin and subsequent changes in mood, including symptoms of depression. With vitamin B6 being the most common nutrient deficiency, and the ever increasing prevalence of depression in the United States, especially among young adults, it is crucial that researchers investigate ways to mitigate both of these undesirable side effects. Current research on the topic fails to directly connect supplementation of vitamin B6 to positive changes in mood in oral contraceptive users. This 12-week long double-blinded, placebo-controlled crossover trial examined the effects of daily supplementation of vitamin B6 as 100 mg of pyridoxine hydrochloride, on mood states in 8 healthy college women (18-25 y) that use combined oral contraceptives. Vitamin status was assessed via plasma pyridoxal 5’-phosphate (PLP). Plasma PLP levels significantly increased by >193% (p=0.003) with daily supplementation of 100 mg B6 over a four week period. Mood changes with supplementation were assessed using the Profile of Mood States (POMS). Although a small improvement in the POMS depression sub score was observed after 4 weeks of vitamin B6 supplementation (14.7%), the changes were insignificant (p>0.05). Furthermore, total mood disturbance scores did not significantly change with either the placebo or supplement periods. While mood states were not improved, a significant decrease in the presence of depressive symptoms as measured by the Beck Depression Inventory was observed after vitamin B6 supplementation, compared to placebo (p=0.047). The results of this study necessitate further investigation into the use of B6 supplementation as a means of reducing negative mood changes in oral contraceptive users. / Dissertation/Thesis / Masters Thesis Nutrition 2020

No description available.

Exercise-induced anaphylaxis (EIA) is a rare severe disease in which patients express asthmatic and allergic symptoms. Little is known about EIA and its pathology. This manuscript presents an hypothesis that combined hormonal (estrogen and progesterone) contraceptive use and stress during puberty alter the immune system and predispose the adult female to EIA. Presented here is what is known about asthma, a much more common disease, and a pilot, experimental paradigm in which EIA is induced in Syrian hamsters. Asthmatic and allergic cases are much more prevalent in pubescent and adult females than in adult males. Women express higher levels of lung inflammation at stages of their lives when estrogen and progesterone levels are at their lowest (i.e., the follicular phase of the menstrual cycle and menopause). Combined birth control pills have been utilized by doctors to treat asthmatic women. Contraceptive treatments maintain steady levels of estrogen and progesterone throughout the menstrual cycle. It is hypothesized that if female hamsters are given constant levels of hormones as well as ovalbumin and exercise challenges during puberty and then have the hormones taken away during adulthood, they will produce abnormal lung sounds and corresponding pathological histology. To test this hypothesis, female Syrian hamsters were treated with ovalbumin, exercise challenge, both and none (the control). They were also treated to maintain constant levels of estrogen and progesterone during puberty. Although the results were inconclusive, the model may demonstrate that constant ovarian hormones, ovalbumin sensitization, and exercise challenges permanently strain the immune system of females in adulthood.

No description available.

INTRODUCTION: Intrauterine devices (IUDs) and implants have been shown to decrease the rate of unintended pregnancies. These methods also known as Long Acting Reversible Contraceptives (LARCs) are considered the birth control of choice for women of childbearing age, including adolescents, from multiple professional medical associations. However, even with strong recommendations, LARCs are widely underused in the United States, especially in rural areas. This research is based in the Rural Health Services Consortium (RHSC) clinic in Rogersville, Tennessee. This research looks at knowledge and use of LARCs in this clinic before and after receiving training in IUD and implant insertion and removal. METHODS: The physicians, nurse practitioners and physician assistants affiliated with the Rural Health Services Consortium were invited to attend both an IUD and an Implant training. Those who agreed to participate in the study were asked to complete a survey, which addressed current knowledge of LARCs, contraceptive counseling practice and LARC referral practice. Surveys were de-identified and linked to each individual provider through a person specific randomized code. Providers were then trained and certified in the insertion and removal of both IUDs and Implants. Following training the providers provided a survey assessing any change in knowledge and intended practice. At three and six months the same providers will be given an additional surveys with their individualized codes. These surveys assessed the providers' knowledge of LARCs and current practice regarding contraceptive counseling and LARC referral. All survey data was compiled and analyzed for statistical significance using paired T tests. Data was analyzed to identify significant changes in knowledge or practice following training. RESULTS: A t-test revealed a statistically significant increase in provider comfort level with discussing the risks and benefits associated with both IUDs (pretest M=1.92, posttest M=2.92, t = -3.09, p<.01) and implants (pretest M = 1.83, posttest M = 2.83, t = -2.76, p< .05). Regarding practice behavior, a t-test found a statistically significant increase in provider recommendation/discussion of Mirena/Skyla (pretest M= 2.09, posttest M= 3.08, t = -2.14, p<.05) and implants (pretest M = 2.25,

No description available.

Current epidemiological data showing that the use of the injectable contraceptive progestin Depotmedroxyprogesterone acetate (DMPA) is associated with increased HIV-1 acquisition is controversial. However, animal and ex vivo data reveal plausible biological mechanisms whereby MPA may increase HIV-1 acquisition. Relatively high levels of endogenous progesterone (P4) found in the luteal phase of the menstrual cycle have also been linked to increased HIV-1 acquisition in animal, clinical and ex vivo models. One of the central hypotheses of the present study was that the mechanism of MPA-induced increase in HIV-1 infection occurs via a different mechanism to that of the luteal phase. Furthermore, MPA has been shown to activate both the glucocorticoid receptor (GR) and its target, the progesterone receptor (PR) isoform B (PR-B), which are both transcription factors and regulate genes involved in immune function. Both the GR and PR are expressed in the cervix, the primary site of heterosexual HIV-1 infection. PR is regulated by endogenous estrogen (E2), of which the concentrations fluctuate throughout the menstrual cycle, and GR expression also varies in response to stress hormones, leading to conditions of varied relative levels of GR/PR. The immune-related consequences of changing the relative levels of GR and PR-B are not well understood. Therefore another hypothesis of this study was that changing the relative levels of GR/PR-B modulates HIV-1 infection and immunomodulatory gene expression in response to the GR/PR agonist, MPA. Since GR and PR-B recognize similar DNA target sequences and may regulate the same genes at the same time, the final hypothesis of the present study was that GR and PR-B reciprocally modulate each other’s activity, through possible association. To investigate the effects of exogenous hormones on HIV-1 infection and mechanisms thereof, peripheral blood mononuclear cells (PBMCs) and TZM-bl cervical cells were used as model systems for HIV-1 infection. These cells were stimulated with P4 and E2 at concentrations mimicking the menstrual cycle phases or with levels of MPA at the upper range of peak serum levels detected in DMPA users. Cells were infected with the R-tropic HIV-1 infectious molecular clone, HIV-1Bal_Renilla and luciferase assays were used to measure HIV-1 infection. Levels of HIV-1 CD4 receptor and CCR5 co-receptor protein or mRNA were measured by flow cytometry or qPCR, respectively, while activation of CD4+ T cells using the activation marker CD69 was measured by flow cytometry in PBMCs. To investigate the effects of changing GR/PR-B levels on HIV-1 infection and immune gene regulation, GR/PR levels were altered in End1/E6E7 immortalized endocervical and HeLa/TZM-bl cervical carcinoma cells by GR siRNA knockdown with or without the simultaneous over-expression of PR-B, and cells were stimulated with MPA or the GR agonist Dexamethasone. mRNA expression iii of key immunomodulatory genes in End1/E6E7 and HeLa cells was measured by qPCR. The modulation of GR activity by PR-B was assessed by promoter-reporter assay in COS1 and U2OS cells over-expressing GR and PR and stimulated with GR- and/or PR-specific ligands. Association of GR and PR-B was measured by co-immunoprecipitation in COS1 and MCF-7 cells, while co-localization of GR and PR-B was measured by confocal microscopy and super-resolution structured illumination microscopy in COS1 cells. MPA significantly increased HIV-1 infection in both PBMCs and TZM-bl cells, while luteal phase hormones did so to a lesser extent. However, MPA but not luteal phase hormones increased the ratio of CD4+/CD8+ T cells in PBMCs. MPA but not luteal phase hormones also increased CCR5 protein expression on CD4+ T cells in PBMCs and total CCR5 mRNA expression in TZM-bl cells. In addition, MPA but not luteal phase hormones increased activation of CD4+ T cells in PBMCs. Using a GR antagonist or GR siRNA, it was shown that the GR but not PR-B is required for MPA-, but not luteal phase hormone-induced increased HIV-1 infection in PBMCs and TZM-bls. The presence of PR-B altered the anti-inflammatory, GR-mediated regulation of some key immunomodulatory genes, including GILZ and IL-6, in End1/E6E7 and HeLa cells in response to MPA. In general, basal (unliganded) expression of immunomodulatory genes exhibited a pro-inflammatory profile in the presence of PR-B. Co-immunoprecipitation assays showed that GR and PR-B appeared to associate. Confocal microscopy suggested GR and PR co-localized in the nucleus in response to GR- and/or PRspecific ligands, while super-resolution microscopy showed that co-localization occurred in select regions within the nucleus. Taken together, MPA increases HIV-1 infection in a manner different from that of luteal phase hormones, most likely involving increased CD4+ T cell frequency (CD4+/CD8+ ratio), activation and increased expression of CCR5 on CD4+ T cells, and requiring the GR. Furthermore, PR-B modulates GR-mediated immune function gene regulation, via potential association and region-specific nuclear co-localization. This suggests that the relative levels of GR/PR may play an important role in determining the inflammatory and immune responses and HIV-1 infection in HIV-1 target cells, both in DMPA users and women not using hormonal contraception.

Introduction: Federally qualified health centers (FQHCs) and health departments (HDs) are essential in providing contraceptive care and ensuring reproductive autonomy for adolescents. Through offering adolescent-specific services and by training providers in adolescent-specific care and patient-centered contraceptive counseling, clinics can ensure access to high quality contraceptive care for adolescents. Despite the significant decrease in adolescent pregnancy rates, rates remain high in the South and in rural counties, suggesting that clinics in these areas may not have the capacity to provide adolescent-specific services and patient-centered counseling. This study compares the capacity to provide adolescent-specific and patient-centered contraceptive services in rural and urban FQHCs and HDs in two southeastern states -- South Carolina (SC) and Alabama (AL). Methods: Data were collected from a statewide survey of FQHC and HD clinics in SC and AL in 2020. A total of 239 clinics were included (FQHC N=112 and HD N=127) and were identified as rural (N=101) or urban (N=138) using Rural-Urban Continuum Codes. Capacity to provide patient-centered adolescent care is defined as 1) a clinic offering adolescent-specific services; 2) providers at the clinic receiving training in patient-centered counseling; and 3) providers receiving training in adolescent-specific care. To measure capacity, these three survey items were dichotomized into Yes/No responses and then combined into a new variable to measure clinics who responded Yes to each survey item. The type of adolescent-specific services was also measured as being onsite, offsite, outreach, or none. Capacity to provide patient-centered adolescent care was compared across clinics located in rural and urban settings and by clinic type. Statistical differences were determined using the Chi-Square test of independence (α= 0.05). Results: Overall, 44.8% of participating clinics in SC and AL had the capacity to provide patient-centered adolescent contraceptive services. Approximately 51.8% of rural and 66.1% of urban HDs reported the capacity to provide adolescent-specific services. In contrast, 26.7% of rural and 35.4% of urban FQHCs reported the capacity to provide adolescent-specific services. Approximately 55.4% of rural and 71.4% of urban HDs provided any adolescent-specific services, but fewer rural HDs (30.2%) provided onsite services than urban HDs (59.3%) (p=0.003). Fewer than half of rural (42.2%) and urban (48.8%) FQHCs provided adolescent-specific services, with approximately 23.8% of rural and 27.9% of urban sites providing onsite services. Conclusions: The capacity of clinics in SC and AL to provide contraceptive counseling to adolescents, which is anchored in reproductive autonomy, is contingent upon the provision of adolescent-specific services and provider training. Most clinics, especially rural clinics, did not have the capacity to provide patient-centered contraceptive counseling to adolescents. This gap in services may contribute to the higher adolescent pregnancy rates in rural areas of SC and AL. Clinics in SC and AL, especially FQHCs, should develop policies that support adolescent-specific contraceptive services and provider training.