Women who use hormonal contraceptives have been shown to report more intense affective responses to partner infidelity than women with a natural cycle. Also, previous research suggests that female jealousy is sensitive to hormonal changes when naturally cycling, with a peak around ovulation, while women using hormonal contraceptives are less sensitive. This research is aimed at exploring women`s perception of couple conflicts in line with predictions derived from evolutionary theory. A factor analysis yielded four dimensions within 19 couple conflicts that were related to jealousy, emotional support, time and effort, and commitment. We tested the hypotheses that women who use hormonal contraceptives will react more strongly to jealousy-provoking scenarios and overall conflicts compared to women with a natural menstrual cycle. We also tested the hypotheses that naturally cycling women would show an increase in their emotional response to jealousy-provoking scenarios at days with high fertility risk. We expected that their emotional response to the scenarios infidelity, lack of emotional support, time and effort and lack of commitment, would increase if they perceived their partners as attractive. By using an online questionnaire, we followed women who were currently in a relationship with age ranging from 18 to 30 years weekly for 12 weeks. Results show a significant difference between women using hormonal contraceptives and naturally cycling women. Women using hormonal contraceptives responded to be more upset by scenarios indicating infidelity, than did naturally cycling women (p < .05), but not on the overall conflicts. However, some unexpected differences on the single scenarios where discovered. For the analysis concerning the fertility-effect, no significant main effect was found. However, our hypotheses were not supported (p > .001), Our results did, however, reveal a non-significant trending in the predicted direction indicating that the partner`s attractiveness interact with fertility status and affect how women respond to situations regarding Jealousy and couple conflicts.

A ocorrência de trombose está freqüentemente associada com a presença de um ou mais fatores de riscos, os quais podem ser genéticos e/ou adquiridos, tais como as mudanças hormonais que ocorrem durante a gravidez, a terapia de reposição hormonal e o uso de contraceptivos hormonais combinados (CHC). A inflamação, por sua vez, é uma importante resposta do organismo às agressões e envolve vários mecanismos biológicos relacionados entre si e altamente regulados, tais como: coagulação, fibrinólise, ativação do sistema complemento (SC), antioxidação e regulação hormonal. Fisiologicamente, os sistemas complemento e da coagulação compartilham componentes. A ativação do fator XII da coagulação é controlada pela mesma proteína reguladora da ativação do sistema complemento, o inibidor de C1. A deficiência do inibidor de C1 leva a uma patologia conhecida como angioedema hereditário. No entanto, uma manifestação clínica similar ao angioedema tem sido descrita em mulheres que usam CHC ou recebem terapia de reposição hormonal com estrogênio (E). Esta influência do estrogênio na coagulação e no SC também é evidenciada pela ação regulatória do E sobre a expressão do fator XII e dos seus níveis plasmáticos. Considerando o efeito pleiotrópico do E, e as interações do SC e da hemostasia, o objetivo desse estudo foi avaliar o efeito de diferentes CHC sobre: a) a atividade hemolítica (AH) do SC e ativação das vias clássica/lectina e alternativa; b) a atividade opsonizante do SC em mediar o burst oxidativo dos neutrófilos; e c) a função dos receptores para complemento (CR) em mediar o burst oxidativo dos neutrófilos. Nós estudamos 5 CHC diferentes e observamos que a) drospirenona + 30g E mostrou uma tendência a aumentar o burst oxidativo mediado por CR; b) gestodeno + 20g E mostrou redução da capacidade opsonizante do SC; c) levonorgestrel + 30g E e gestodeno + 20g E promoveram uma redução no número de neutrófilos positivos para a expressão de CR1; d) drospirenona + 30g E e drospirenona + 20g E promoveram um aumento da AH da via clássica (VC) do SC; e) levonorgestrel + 30g E promoveu uma redução da AH da VC do SC; f) drospirenona + 30g E, gestodeno + 20g E e levonorgestrel + 30g E promoveram uma diminuição do nível sérico de C4d, produto da ativação das vias clássica/lectina do SC; g) levonorgestrel + 30g E apresentou um aumento da concentração sérica de inibidor de C1; h) nenhum dos CHC mostrou diferenças na ativação da via alternativa do SC. Os resultados mostram a importância de considerar os diferentes grupos de CHC nas comparações com o Grupo Controle, uma vez que algumas diferenças foram significativas apenas para CHC em particular. Estas observações podem contribuir para o entendimento dos mecanismos envolvidos na fisiopatologia dos processos inflamatórios associados ao uso de estrogênios. / The occurrence of thrombosis is often associated with the presence of one or more risk factors, which may be genetic and/or acquired, such as hormonal changes that occur during pregnancy, hormone replacement therapy and the use of combined hormonal contraceptives (CHC). The inflammation in turn, is an important body\'s response to the aggression and involves several biological mechanisms related and highly regulated, such as coagulation, fibrinolysis, activation of the complement system (CS), oxidation and hormonal regulation. Physiologically, the complement and coagulation systems share components. Activation of coagulation factor XII is controlled by the same regulatory protein activation of the complement inhibitor C1. The deficiency of C1 inhibitor leads to a condition known as hereditary angioedema. However, a clinical manifestation similar to angioedema has been reported in women using CHC or receiving hormone replacement therapy with estrogen (E). The influence of E on coagulation and the CS is also evidenced by the regulatory action of E on the expression of factor XII and its plasma levels. Considering the pleiotropic effects of E, and the interactions of CS and hemostasis, the goal of this study was to evaluate the effect of different CHC on: a) hemolytic activity (HA) CS and activation of classical/lectin and alternative pathways, b) the opsonizing activity of the CS in mediating the oxidative burst of neutrophils, and c) the function of receptors for complement (CR) in mediating the oxidative burst (OB) of neutrophils. We studied 5 different CHC and data showed: a) drospirenone + 30g E increase of the OB neutrophils mediated by CR; b) gestodene + 20g E had a reduced opsonizing ability; c) levonorgestrel + 30g E and gestodene + 20g E promoted a reduction of neutrophils positive for the expression of CR1, d) drospirenone + 30g E and drospirenone + 20g E promoted an increase in HA for classical pathway (CP); e) levonorgestrel + 30g E reduced the HA for CP; f) drospirenone + 30g E and gestodene + 20g E and levonorgestrel + 30g E reduced the serum level of C4d; g) levonorgestrel + 30g E showed an increase of the serum level of C1 inhibitor; h) none of CHC showed differences in activation of the alternative pathway in CS. The results show the importance of considering the different groups of CHC in comparison with the control group, since some differences were significant only for CHC in particular. These observations may contribute to the understanding of the mechanisms involved in the pathophysiology of inflammatory processes associated with estrogen use.

A ocorrência de trombose está freqüentemente associada com a presença de um ou mais fatores de riscos, os quais podem ser genéticos e/ou adquiridos, tais como as mudanças hormonais que ocorrem durante a gravidez, a terapia de reposição hormonal e o uso de contraceptivos hormonais combinados (CHC). A inflamação, por sua vez, é uma importante resposta do organismo às agressões e envolve vários mecanismos biológicos relacionados entre si e altamente regulados, tais como: coagulação, fibrinólise, ativação do sistema complemento (SC), antioxidação e regulação hormonal. Fisiologicamente, os sistemas complemento e da coagulação compartilham componentes. A ativação do fator XII da coagulação é controlada pela mesma proteína reguladora da ativação do sistema complemento, o inibidor de C1. A deficiência do inibidor de C1 leva a uma patologia conhecida como angioedema hereditário. No entanto, uma manifestação clínica similar ao angioedema tem sido descrita em mulheres que usam CHC ou recebem terapia de reposição hormonal com estrogênio (E). Esta influência do estrogênio na coagulação e no SC também é evidenciada pela ação regulatória do E sobre a expressão do fator XII e dos seus níveis plasmáticos. Considerando o efeito pleiotrópico do E, e as interações do SC e da hemostasia, o objetivo desse estudo foi avaliar o efeito de diferentes CHC sobre: a) a atividade hemolítica (AH) do SC e ativação das vias clássica/lectina e alternativa; b) a atividade opsonizante do SC em mediar o burst oxidativo dos neutrófilos; e c) a função dos receptores para complemento (CR) em mediar o burst oxidativo dos neutrófilos. Nós estudamos 5 CHC diferentes e observamos que a) drospirenona + 30g E mostrou uma tendência a aumentar o burst oxidativo mediado por CR; b) gestodeno + 20g E mostrou redução da capacidade opsonizante do SC; c) levonorgestrel + 30g E e gestodeno + 20g E promoveram uma redução no número de neutrófilos positivos para a expressão de CR1; d) drospirenona + 30g E e drospirenona + 20g E promoveram um aumento da AH da via clássica (VC) do SC; e) levonorgestrel + 30g E promoveu uma redução da AH da VC do SC; f) drospirenona + 30g E, gestodeno + 20g E e levonorgestrel + 30g E promoveram uma diminuição do nível sérico de C4d, produto da ativação das vias clássica/lectina do SC; g) levonorgestrel + 30g E apresentou um aumento da concentração sérica de inibidor de C1; h) nenhum dos CHC mostrou diferenças na ativação da via alternativa do SC. Os resultados mostram a importância de considerar os diferentes grupos de CHC nas comparações com o Grupo Controle, uma vez que algumas diferenças foram significativas apenas para CHC em particular. Estas observações podem contribuir para o entendimento dos mecanismos envolvidos na fisiopatologia dos processos inflamatórios associados ao uso de estrogênios. / The occurrence of thrombosis is often associated with the presence of one or more risk factors, which may be genetic and/or acquired, such as hormonal changes that occur during pregnancy, hormone replacement therapy and the use of combined hormonal contraceptives (CHC). The inflammation in turn, is an important body\'s response to the aggression and involves several biological mechanisms related and highly regulated, such as coagulation, fibrinolysis, activation of the complement system (CS), oxidation and hormonal regulation. Physiologically, the complement and coagulation systems share components. Activation of coagulation factor XII is controlled by the same regulatory protein activation of the complement inhibitor C1. The deficiency of C1 inhibitor leads to a condition known as hereditary angioedema. However, a clinical manifestation similar to angioedema has been reported in women using CHC or receiving hormone replacement therapy with estrogen (E). The influence of E on coagulation and the CS is also evidenced by the regulatory action of E on the expression of factor XII and its plasma levels. Considering the pleiotropic effects of E, and the interactions of CS and hemostasis, the goal of this study was to evaluate the effect of different CHC on: a) hemolytic activity (HA) CS and activation of classical/lectin and alternative pathways, b) the opsonizing activity of the CS in mediating the oxidative burst of neutrophils, and c) the function of receptors for complement (CR) in mediating the oxidative burst (OB) of neutrophils. We studied 5 different CHC and data showed: a) drospirenone + 30g E increase of the OB neutrophils mediated by CR; b) gestodene + 20g E had a reduced opsonizing ability; c) levonorgestrel + 30g E and gestodene + 20g E promoted a reduction of neutrophils positive for the expression of CR1, d) drospirenone + 30g E and drospirenone + 20g E promoted an increase in HA for classical pathway (CP); e) levonorgestrel + 30g E reduced the HA for CP; f) drospirenone + 30g E and gestodene + 20g E and levonorgestrel + 30g E reduced the serum level of C4d; g) levonorgestrel + 30g E showed an increase of the serum level of C1 inhibitor; h) none of CHC showed differences in activation of the alternative pathway in CS. The results show the importance of considering the different groups of CHC in comparison with the control group, since some differences were significant only for CHC in particular. These observations may contribute to the understanding of the mechanisms involved in the pathophysiology of inflammatory processes associated with estrogen use.

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)

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)

Background: Black South African women are known to have a high usage rate of injectable contraceptives. Breast cancer is the second leading cancer after malignant cervical neoplasms in black South African women. There is evidence that sex hormones are associated with an increased risk of developing breast cancer. In the Western Cape, investigators suggested that injectable contraceptives, more specifically DMPA, may increase breast cancer risk. In another study conducted in the same province, a weak association between breast cancer and women taking combined oestrogen/progesterone oral contraceptives was found, though no risk associated with injectable progestogen contraceptives (DMPA) was confirmed. Study Objective: This study aimed to determine whether there is an association between hormonal contraceptive use and an increased risk of cancer of the breast. Methods: Data was obtained from an ongoing case control study set up by MRC/Wits/NHLS Cancer Epidemiology Research Group (CERG) in 1995 to investigate risk factors associated with cancer among the black population in Johannesburg. Data was processed using STATA, version8 and analysed using univariate, bivariate and multivariate unmatched logistic regression models. Results: There was evidence that an overall use of oral contraceptives increases the risk of breast cancer; cases (n= 221), controls :( n= 153), OR=2.01 (95% CI:1.45, 2.80), p<0.0001. There was evidence of an association between use of injectable contraception and the risk of breast cancer; cases (n=244), controls (n=202), OR=1.51(CI: 1.14, 2.01),p=0.004 Surprisingly, no other use characteristic of either hormonal contraceptive method was statistically significantly associated with the risk of breast cancer in our dataset. The combined use of both oral and injectable contraception was associated with an increased risk of breast cancer, OR=1.68(1.21, 2.33), p =0.002. There was a strong effect modification (interaction) between oral contraceptive use and injectable progesterone associated with the risk of breast cancer, (p=0.008). Conclusion: After adjusting for all potential risk and confounding factors, as collected in the dataset, there was evidence of an association between combined oral contraceptive use and breast cancer. An association between cancer of the breast and overall use of injectable progesterone use was also established. There was evidence of association between the use of both hormonal contraceptive methods and an increased risk of breast cancer. However, whether these findings reflect the reality in terms of causal relationship or are the result of bias must be ascertained.

The vagina is the port of entry for sexually transmitted diseases in women. Its epithelium constitutes the luminal border, thus comprising an important defence barrier. The objective of this work was to investigate the mechanisms of importance in the immune defence of the vaginal epithelium of healthy, fertile women, and possible menstrual cycle changes. Effects of hormonal contraceptive usage on oestrogen receptor (ER) and progesterone receptor (PR) expression were studied. The contribution of epithelial cell to the immune defence was estimated by assaying their expression of antimicrobial defensins and the epithelial thickness. Vaginal biopsies and serum samples were collected during the follicular and luteal phases in regularly menstruating women (controls) and in users of combined oral contraceptives (COCs), levonorgestrel implants (LNGs), or depot-medroxyprogesterone acetate injections (DMPAs). Fifteen healthy women (aged 20–34 years) were enrolled in each group. Morphometry was performed on vaginal tissue stained with haematoxylin/eosin and by immunohistochemistry using monoclonal antibodies against immune cell markers, PR, and ER. Expression of mRNA for human α-defensins HD-5 and HD-6, and human β-defensins (HBD) 1 to 4 were determined by real-time qRT-PCR and in situ hybridization. In controls, the epithelium was 261 ± 16 μm thick and harboured 241 ± 35 leukocytes (CD45+) per mm2. T lymphocytes (CD3+) dominated. Both αβ T cells and γδ T cells were present with an approximate 4-fold dominance of αβ T cells. Cytotoxic T cells (CD8+) were more frequent than T helper cells (CD4:CD8 ratio: 0.7 ± 0.1). Macrophages (CD68+) constituted the second-largest population, followed by Langerhans cells (CD1a+). B cells, natural killer cells, monocytes and granulocytes were generally absent. No differences were found between the follicular and luteal phase. All four β-defensins analysed for were detected in vaginal epithelium and most samples expressed at least two. HBD-2 and HBD-3 were most frequent. HBD-3 and HBD-4 expressing cells were localized in the parabasal and intermediate cell layers. α-defensins were not detected. The epithelium was significantly thicker (333 ± 9 μm) in COC, LNG, and DMPA users than in controls, and commonly showed hyperplasia. In DMPA and LNG users the frequency of intraepithelial leukocytes (CD45+) was increased, explained by increased frequencies of both αβ and γδ T cells. In DMPA users there was also a selective increase in CD8+ T cells. PR expression was significantly reduced in DMPA users compared with controls, COC and LNG users. COC and particularly DMPA users often had undetectable levels of serum E2. In conclusion, both adaptive immunity, i.e. intraepithelial T cells, and innate defence mechanisms, i.e. intraepithelial macrophages and β-defensins, are believed to contribute to the immune defence in the human female lower genital tract. These parameters did not change during the menstrual cycle but hormonal contraceptive usage, especially DMPA, affected the quality of the epithelium. The use of DMPA and LNG was correlated with the accumulation of T cells within the epithelium. The effects of these changes on the risk of contracting infections are yet to be determined.

Background: Teen pregnancy is associated with an array of negative social and health related outcomes for the mother as well as the baby. The risk of becoming a parent before the age of 20 is clearly elevated for former child welfare clients. Aim: The aim of this study is therefore to investigate the elevated birth rates among female adolescent child welfare clients by examining the relationship between contraceptive behaviour and pregnancies. Method: The study was based on a set of compiled register data. The study population were all females between the ages 14 and 19 during the years 2006-2008 (n. 487 115). The study group of main interest were child welfare clients who were compared to peers in the majority population as well as international and national adoptees. Analysis was conducted with multivariate logistic regression and the observed association was controlled for maternal, socio-demographic and behavioural factors. Results: The two sub-populations of child welfare clients both had much higher rates of retrieved hormonal contraceptives compared to the majority population, the international and the national adoptees up to age 17. In the ages 18 and 19 the rates were instead lower than the majority population. The child welfare clients had a stronger association to births than all groups of comparison, which was consistent with earlier research. All findings persisted after controlling for socio-demographic, maternal and behavioural factors. Conclusion: The child welfare clients showed a specific pattern of contraceptive behaviour over the age groups which was not consistent with the groups of comparison or with the expected relationship to birth rates. This suggests that teenage births cannot unanimously be predicted by the rates of retrieved hormonal contraceptives. The results imply that other factors than those investigated in this study are more influential regarding the contraceptive behaviour of this adolescent population.

Glicosaminoglicanos (GAG) no urotélio e na urina possuem um efeito protetor contra desordens tais com urolitíase e cistite intersticial. Adicionalmente, foi demonstrado que hormônios sexuais femininos podem modular a excreção urinária de GAG (Maroclo M.V. et al. J Urol. 2005;173:1789-92). O presente estudo investigou se os anticoncepcionais hormonais orais combinados (AHOC) influenciam na excreção urinária de GAG. Amostras de urina foram doadas por mulheres jovens que utilizavam anticoncepcionais orais regularmente: EE + D (0,030 mg etinilestradiol + 3,0 mg drosperinona), n=9; EE + C (0,035 mg etinilestradiol + 2,0 mg acetato de ciproterona), n=9; e EE + G (0,020 mg etinilestradiol + 0,075 mg gestodeno), n=7. Controles foram 10 mulheres da mesma faixa etária não usuárias de AHOC. Valores de GAG urinário total das primeira e segunda metades do ciclo menstrual foram expressos como &#956;g ácido hexurônico por mg de creatinina urinária. A proporção de GAG sulfatado foi determinada pela eletroforese em gel de agarose. Em contraste com o grupo controle, a excreção de GAG total na primeira e segunda metades do ciclo menstrual foi bastante similar nos grupos usuários de AHOC. Valores de excreção em todo o ciclo foram maior no grupo usuário de AHOC (p < 0,01), particularmente para o grupo usuário de EE + C, no qual os valores foram o dobro dos valores do controle (p < 0,005). Comparados com o controle, os 3 grupos usuários de AHOC produziram diferenças marcantes na composição urinária de GAG sulfatado, com diminuição de aproximadamente 50% no HS (p < 0,02) e DS (p < 0,02), e um aumento próximo de 100% no CS (p < 0,004). O padrão de excreção urinário de GAG está claramente alterado em mulheres que ingerem os AHOC estudados. Sendo assim, esta mudança na excreção constitui um efeito benéfico adicional dos AHOC, pois ela aumenta o potencial efeito protetor dos GAG contra desordens do trato urinário. / Glycosaminoglycans (GAG) on the urothelium and in the urine have protective effects against disorders such as urolithiasis and interstitial cystitis. Additionally, we have shown that female sex hormones may modulate urinary GAG excretion (Maroclo MV et al. J Urol 2005;173:1789-92). Here we investigated whether oral hormonal contraceptives (OC) affect urinary GAG excretion. Urine specimens were obtained from young women regularly taking the following OC: EE + D (0.030 mg ethinyl estradiol + 3.0 mg drospirenone), n=9; EE + C (0.035 mg ethinyl estradiol + 2.0 mg cyproterone acetate), n=9; and EE + G (0.020 mg ethinyl estradiol + 0.075 mg gestodene), n=7. Controls were from ten age-matched women not taking OC. Total urinary GAG from the first and second halves of the menstrual cycle was assayed as g hexuronic acid per mg urinary creatinine. Content of sulfated GAG species was determined by agarose gel electrophoresis. In contrast to controls, excretion of total GAG in the first and second halves of the menstrual cycle was quite similar in the OC groups. Excretion values for the whole cycle were higher in the OC groups (p < 0.01), especially for EE + C, in which the values were twice those from controls (p < 0.005). Compared with controls, the three OC produced marked changes in the composition of urinary sulfated GAG, with decreases of ~50% in HS (p < 0.02) and DS (p < 0.02), and a ~100% increase in CS (p < 0.004). The pattern of urinary GAG excretion is clearly changed in women taking commonly used OC. However, this altered excretion should constitute an additional beneficial effect of OC, as it enhances the protective effects of GAG against urinary tract disorders.

Glicosaminoglicanos (GAG) no urotélio e na urina possuem um efeito protetor contra desordens tais com urolitíase e cistite intersticial. Adicionalmente, foi demonstrado que hormônios sexuais femininos podem modular a excreção urinária de GAG (Maroclo M.V. et al. J Urol. 2005;173:1789-92). O presente estudo investigou se os anticoncepcionais hormonais orais combinados (AHOC) influenciam na excreção urinária de GAG. Amostras de urina foram doadas por mulheres jovens que utilizavam anticoncepcionais orais regularmente: EE + D (0,030 mg etinilestradiol + 3,0 mg drosperinona), n=9; EE + C (0,035 mg etinilestradiol + 2,0 mg acetato de ciproterona), n=9; e EE + G (0,020 mg etinilestradiol + 0,075 mg gestodeno), n=7. Controles foram 10 mulheres da mesma faixa etária não usuárias de AHOC. Valores de GAG urinário total das primeira e segunda metades do ciclo menstrual foram expressos como &#956;g ácido hexurônico por mg de creatinina urinária. A proporção de GAG sulfatado foi determinada pela eletroforese em gel de agarose. Em contraste com o grupo controle, a excreção de GAG total na primeira e segunda metades do ciclo menstrual foi bastante similar nos grupos usuários de AHOC. Valores de excreção em todo o ciclo foram maior no grupo usuário de AHOC (p < 0,01), particularmente para o grupo usuário de EE + C, no qual os valores foram o dobro dos valores do controle (p < 0,005). Comparados com o controle, os 3 grupos usuários de AHOC produziram diferenças marcantes na composição urinária de GAG sulfatado, com diminuição de aproximadamente 50% no HS (p < 0,02) e DS (p < 0,02), e um aumento próximo de 100% no CS (p < 0,004). O padrão de excreção urinário de GAG está claramente alterado em mulheres que ingerem os AHOC estudados. Sendo assim, esta mudança na excreção constitui um efeito benéfico adicional dos AHOC, pois ela aumenta o potencial efeito protetor dos GAG contra desordens do trato urinário. / Glycosaminoglycans (GAG) on the urothelium and in the urine have protective effects against disorders such as urolithiasis and interstitial cystitis. Additionally, we have shown that female sex hormones may modulate urinary GAG excretion (Maroclo MV et al. J Urol 2005;173:1789-92). Here we investigated whether oral hormonal contraceptives (OC) affect urinary GAG excretion. Urine specimens were obtained from young women regularly taking the following OC: EE + D (0.030 mg ethinyl estradiol + 3.0 mg drospirenone), n=9; EE + C (0.035 mg ethinyl estradiol + 2.0 mg cyproterone acetate), n=9; and EE + G (0.020 mg ethinyl estradiol + 0.075 mg gestodene), n=7. Controls were from ten age-matched women not taking OC. Total urinary GAG from the first and second halves of the menstrual cycle was assayed as g hexuronic acid per mg urinary creatinine. Content of sulfated GAG species was determined by agarose gel electrophoresis. In contrast to controls, excretion of total GAG in the first and second halves of the menstrual cycle was quite similar in the OC groups. Excretion values for the whole cycle were higher in the OC groups (p < 0.01), especially for EE + C, in which the values were twice those from controls (p < 0.005). Compared with controls, the three OC produced marked changes in the composition of urinary sulfated GAG, with decreases of ~50% in HS (p < 0.02) and DS (p < 0.02), and a ~100% increase in CS (p < 0.004). The pattern of urinary GAG excretion is clearly changed in women taking commonly used OC. However, this altered excretion should constitute an additional beneficial effect of OC, as it enhances the protective effects of GAG against urinary tract disorders.