Samie, A.Traore, N. A.Manavhela, Murendeni2025-10-092025-10-092025-09-05Manavhela, M. 2025. Ethinylestradiol (EE2) and Human Reproductive Health: Investigating the Potential Effects of Contraceptives on Human Reproductive Health and Sexually Transmitted Diseases in the Era of HIV and AIDS. . .https://univendspace.univen.ac.za/handle/11602/2992PhD (Microbiology)Department of Biochemistry and MicrobiologyBackground: Reproduction and sexual health are fundamental aspects of human life and are influenced by various hormones, including sex steroids. Sex steroids, estrogen in particular have been implicated in numerous human health issues. The association between estrogens and sexually transmitted diseases (STIs) is not clear as studies are contradictory; other studies suggest that estrogens confer protection against STIs and others report that they facilitate the progression of STIs. Because of the extensive use of Ethinylestradiol (EE2) in birth control, it has now become a major global pollutant due to its presence in wastewater, either through household waste, agricultural waste or through industrial wastes. In the aquatic environments where wastewater is discharged, there is a wide variety of organisms that reside there, and in the end they become victims of the impact the hormones has have on them. It’s been reported that exposure of aquatic organisms to estrogens has been linked to endocrine disruption, including feminization, and these changes are correlated with EE2 concentrations. While extensive research has been on the ecological consequences of EE2, there remains a gap in understanding the impact of estrogens in human health, particularly synthetic estrogens. Given the widespread environmental distribution of these hormones, further research is necessary to elucidate their potential effects on human reproductive health, particularly in relation to sexually transmitted infection (STIs). Aims and Objectives: The main aim of the study was to further our understanding of the potential impacts of birth control and the tools used particularly ethinylestradiol on sexual health and sexually transmitted infections. A number of objectives were identified and included: 1. To assess the knowledge, attitude, and practices of contraceptives amongst women of reproductive age. 2. To determine the prevalence of contraceptive use amongst women of reproductive age. 3. To describe contraception association with sexually transmitted diseases. 4. To identify microorganisms causing sexually transmitted infections among study participants (Neisseria gonorrhea, Chlamydia trachomatis and Trichomonas vaginalis). 5. To determine ethinylestradiol concentration in the study population. 6. To assess the potential association between contraceptive use and UTI. 7. Provide insight into urine metabolomics across study participants using different birth control methods. Methods: A community based cross-sectional study was conducted in Northern Limpopo, in the Vhembe district. A paper-based questionnaire was used to collect data such as demographic data, knowledge, attitude and practice of women of reproductive age towards contraceptives. Urine samples were collected from the study participants using sterile sample collection containers. In the laboratory, urine samples were cultured for UTI determination. Enzyme-linked immunosorbent assay (ELISA) was used to quantify Ethinylestradiol (EE2) concentration from the samples. Polymerase Chain Reaction (PCR) was used for detection of three different microorganisms causing non-viral sexually transmitted infections including Chlamydia trachomatis, Neisseria gonorrhea and Trichomonas vaginalis. For metabolite extraction, solid phase extraction (SPE) was used to extract metabolites from urine samples using C18-E silica- based cartridges. Collected data was entered and cleaned on excel spread sheet. SPSS software V27 and Stata V12 were used to analyze the data (descriptive statistics was used to estimate frequencies and chi-square test was used for examine associations). Metabolomics data was analyzed using MetaboAnalyst 6.0 online software. Results: Of the 364 women who participated in the study, 96.11% were aware of what contraceptives are. Participants acquired knowledge through more than one platform, with 41.67% through media, 41.38% via health care workers and 31.61% through social media networks. Participants had knowledge of at least one method of contraception. In practice, 75.1% were using at least one form of contraceptive and the most common methods were injectables (46.1%), male condoms (23.8%), and pills (17.4%). Most participants (96.9%) had a positive attitude towards contraceptives and 94.4% said they think contraceptives are beneficial, while 79.8% agreed that the main benefit is to avoid unwanted pregnancy. Chlamydia trachomatis was the most common STI with a prevalence of (17.39%), followed by Neisseria gonorrhea with a prevalence of (5.43%) and Trichomonas vaginalis with a prevalence of (2.72%). Based on the age group, N. gonorrhea had the highest rate of (75.0%), followed by C. trachomatis with (59.68%) and then T. vaginalis with a prevalence rate of (30.0%) in participants who were aged between 20-30 years. Educational status appeared to have an influence on the prevalence of N. gonorrhea showing the highest infection rate of (55.0%) in individual’s who studied up to tertiary level as well as C. trachomatis (53.33%) and T. vaginalis (50.0%) in those with high school education. Coinfections with C. trachomatis and N. gonorrhea were observed in (30.0%) of the participants. Urinary tract infections (UTIs) were detected in 34.2% of the study population. Education did not seem to reduce the impact of UTIs among the study participants. UTIs were statistically significant among patients who had been using contraceptives for a long time and also among patients who were using Intrauterine devices as contraceptive method particularly (p value less than 0.05. UTIS were also common among participants who had experienced miscarriage although the difference was not statistically significant. The presence of blood, nitrate and ketones in the urine samples were significant markers of UTI among the study participants. The concentration of ethinylestradiol varied across the samples from low concentration of 11pg/ml to the highest concentration of 804 pg/ml. The concentration of EE2 varied with age, marital status and education level. Individuals with higher educational level also seemed to have higher concentration of EE2 in their urine samples. There was a statistically significant association between ethinylestradiol occurrence and urinary tract infection (UTI) with p value of 0.006. However, there was no significant association with the three STDs tested, although more samples positive for the infection tended to be positive for EE2. Individuals who had experienced miscarriage tended to have higher concentrations of EE2 although the difference was not statistically significant. Metabolomics studyies identified a number of compounds in the urine samples. The metabolites identified were mostly associated with lipid metabolism changes, hormonal and estrogenic activity, inflammation and immune responses. Metabolites with neurological impact were also detected. Some of these metabolites included but are not limited to Equol, Pergolide, Leukotriene and Scopamine. Conclusion: We observed a high rate of awareness towards family planning methods. However, there is still a need for improvement in terms of translating the information into practice. Although, women of reproductive age were the primary focus, regular screening for sexually transmitted infections (STIs) should be expanded to other significant groups such as sex workers and men who have sex with men (MSM). Ethinylestradiol (EE2) can be detected in individuals beyond those actively using EE2-containing contraceptives; however, prolonged use of such contraceptives may contribute to elevated levels of EE2 in urine samples over time.Ethinylestradiol (EE2) is not only found in individuals who are using ethinylestradiol-containing contraception, however, long term usage of contraceptive might increase the chances of increased EE2 in the urine samples. However, there is need for further studies to understand the origins of the synthetic compound as there are external factors contributing to levels of the synthetic compound in the body. Furthermore, variation of urine metabolomics is dependent on individual physiology and could be used as biomarkers for lifestyle factors, drug response and to monitor diseases.1 online resource ()enUniversity of VendaUCTDThesisManavhela M. Ethinylestradiol (EE2) and Human Reproductive Health: Investigating the Potential Effects of Contraceptives on Human Reproductive Health and Sexually Transmitted Diseases in the Era of HIV and AIDS. []. , 2025 [cited yyyy month dd]. Available from:Manavhela, M. (2025). <i>Ethinylestradiol (EE2) and Human Reproductive Health: Investigating the Potential Effects of Contraceptives on Human Reproductive Health and Sexually Transmitted Diseases in the Era of HIV and AIDS</i>. (). . Retrieved fromManavhela, Murendeni. <i>"Ethinylestradiol (EE2) and Human Reproductive Health: Investigating the Potential Effects of Contraceptives on Human Reproductive Health and Sexually Transmitted Diseases in the Era of HIV and AIDS."</i> ., , 2025.TY - Thesis AU - Manavhela, Murendeni AB - Background: Reproduction and sexual health are fundamental aspects of human life and are influenced by various hormones, including sex steroids. Sex steroids, estrogen in particular have been implicated in numerous human health issues. The association between estrogens and sexually transmitted diseases (STIs) is not clear as studies are contradictory; other studies suggest that estrogens confer protection against STIs and others report that they facilitate the progression of STIs. Because of the extensive use of Ethinylestradiol (EE2) in birth control, it has now become a major global pollutant due to its presence in wastewater, either through household waste, agricultural waste or through industrial wastes. In the aquatic environments where wastewater is discharged, there is a wide variety of organisms that reside there, and in the end they become victims of the impact the hormones has have on them. It’s been reported that exposure of aquatic organisms to estrogens has been linked to endocrine disruption, including feminization, and these changes are correlated with EE2 concentrations. While extensive research has been on the ecological consequences of EE2, there remains a gap in understanding the impact of estrogens in human health, particularly synthetic estrogens. Given the widespread environmental distribution of these hormones, further research is necessary to elucidate their potential effects on human reproductive health, particularly in relation to sexually transmitted infection (STIs). Aims and Objectives: The main aim of the study was to further our understanding of the potential impacts of birth control and the tools used particularly ethinylestradiol on sexual health and sexually transmitted infections. A number of objectives were identified and included: 1. To assess the knowledge, attitude, and practices of contraceptives amongst women of reproductive age. 2. To determine the prevalence of contraceptive use amongst women of reproductive age. 3. To describe contraception association with sexually transmitted diseases. 4. To identify microorganisms causing sexually transmitted infections among study participants (Neisseria gonorrhea, Chlamydia trachomatis and Trichomonas vaginalis). 5. To determine ethinylestradiol concentration in the study population. 6. To assess the potential association between contraceptive use and UTI. 7. Provide insight into urine metabolomics across study participants using different birth control methods. Methods: A community based cross-sectional study was conducted in Northern Limpopo, in the Vhembe district. A paper-based questionnaire was used to collect data such as demographic data, knowledge, attitude and practice of women of reproductive age towards contraceptives. Urine samples were collected from the study participants using sterile sample collection containers. In the laboratory, urine samples were cultured for UTI determination. Enzyme-linked immunosorbent assay (ELISA) was used to quantify Ethinylestradiol (EE2) concentration from the samples. Polymerase Chain Reaction (PCR) was used for detection of three different microorganisms causing non-viral sexually transmitted infections including Chlamydia trachomatis, Neisseria gonorrhea and Trichomonas vaginalis. For metabolite extraction, solid phase extraction (SPE) was used to extract metabolites from urine samples using C18-E silica- based cartridges. Collected data was entered and cleaned on excel spread sheet. SPSS software V27 and Stata V12 were used to analyze the data (descriptive statistics was used to estimate frequencies and chi-square test was used for examine associations). Metabolomics data was analyzed using MetaboAnalyst 6.0 online software. Results: Of the 364 women who participated in the study, 96.11% were aware of what contraceptives are. Participants acquired knowledge through more than one platform, with 41.67% through media, 41.38% via health care workers and 31.61% through social media networks. Participants had knowledge of at least one method of contraception. In practice, 75.1% were using at least one form of contraceptive and the most common methods were injectables (46.1%), male condoms (23.8%), and pills (17.4%). Most participants (96.9%) had a positive attitude towards contraceptives and 94.4% said they think contraceptives are beneficial, while 79.8% agreed that the main benefit is to avoid unwanted pregnancy. Chlamydia trachomatis was the most common STI with a prevalence of (17.39%), followed by Neisseria gonorrhea with a prevalence of (5.43%) and Trichomonas vaginalis with a prevalence of (2.72%). Based on the age group, N. gonorrhea had the highest rate of (75.0%), followed by C. trachomatis with (59.68%) and then T. vaginalis with a prevalence rate of (30.0%) in participants who were aged between 20-30 years. Educational status appeared to have an influence on the prevalence of N. gonorrhea showing the highest infection rate of (55.0%) in individual’s who studied up to tertiary level as well as C. trachomatis (53.33%) and T. vaginalis (50.0%) in those with high school education. Coinfections with C. trachomatis and N. gonorrhea were observed in (30.0%) of the participants. Urinary tract infections (UTIs) were detected in 34.2% of the study population. Education did not seem to reduce the impact of UTIs among the study participants. UTIs were statistically significant among patients who had been using contraceptives for a long time and also among patients who were using Intrauterine devices as contraceptive method particularly (p value less than 0.05. UTIS were also common among participants who had experienced miscarriage although the difference was not statistically significant. The presence of blood, nitrate and ketones in the urine samples were significant markers of UTI among the study participants. The concentration of ethinylestradiol varied across the samples from low concentration of 11pg/ml to the highest concentration of 804 pg/ml. The concentration of EE2 varied with age, marital status and education level. Individuals with higher educational level also seemed to have higher concentration of EE2 in their urine samples. There was a statistically significant association between ethinylestradiol occurrence and urinary tract infection (UTI) with p value of 0.006. However, there was no significant association with the three STDs tested, although more samples positive for the infection tended to be positive for EE2. Individuals who had experienced miscarriage tended to have higher concentrations of EE2 although the difference was not statistically significant. Metabolomics studyies identified a number of compounds in the urine samples. The metabolites identified were mostly associated with lipid metabolism changes, hormonal and estrogenic activity, inflammation and immune responses. Metabolites with neurological impact were also detected. Some of these metabolites included but are not limited to Equol, Pergolide, Leukotriene and Scopamine. Conclusion: We observed a high rate of awareness towards family planning methods. However, there is still a need for improvement in terms of translating the information into practice. Although, women of reproductive age were the primary focus, regular screening for sexually transmitted infections (STIs) should be expanded to other significant groups such as sex workers and men who have sex with men (MSM). Ethinylestradiol (EE2) can be detected in individuals beyond those actively using EE2-containing contraceptives; however, prolonged use of such contraceptives may contribute to elevated levels of EE2 in urine samples over time.Ethinylestradiol (EE2) is not only found in individuals who are using ethinylestradiol-containing contraception, however, long term usage of contraceptive might increase the chances of increased EE2 in the urine samples. However, there is need for further studies to understand the origins of the synthetic compound as there are external factors contributing to levels of the synthetic compound in the body. Furthermore, variation of urine metabolomics is dependent on individual physiology and could be used as biomarkers for lifestyle factors, drug response and to monitor diseases. DA - 2025-09-05 DB - ResearchSpace DP - Univen LK - https://univendspace.univen.ac.za PY - 2025 T1 - Ethinylestradiol (EE2) and Human Reproductive Health: Investigating the Potential Effects of Contraceptives on Human Reproductive Health and Sexually Transmitted Diseases in the Era of HIV and AIDS TI - Ethinylestradiol (EE2) and Human Reproductive Health: Investigating the Potential Effects of Contraceptives on Human Reproductive Health and Sexually Transmitted Diseases in the Era of HIV and AIDS UR - ER -