Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver.

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

Oral contraceptive use increases risk of inflammatory and coagulatory disorders in women with Polycystic Ovarian Syndrome: An observational study.

Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women. 50 subjects diagnosed with Rotterdam criteria receiving no drug treatment served as controls whereas 50 subjects receiving only OCPs (Ethinyl estradiol 0.03 mg, Levonorgestrel 0.15 mg) as a mode of treatment at least for six-months served as cases. Ferriman-Gallwey score and hormonal profile improved on OCP treatment. However, parameters like weight, Body mass index, waist-hip ratio, Oral glucose tolerance test, lipid profile, insulin, HOMA-IR, adiponectin, interleukin1ß, visfatin, resistin, tissue factor, PT and APTT showed considerable derangements in OCP group. All above parameters are associated with the risk of diabetes mellitus, dyslipidemia, coronary vascular disease, cancers, hypercoagulable state, venous thromboembolism and thrombotic events. Long-term use of OCPs needs to be considered carefully for PCOS patients who are already burdened with associated risk factors. This study was conducted in a region where women do not have much access to high-end screening and diagnostic facilities that further exacerbates their clinical outcomes. Large scale, long-term studies need to be designed to further evaluate safety use of OCPs in PCOS women.

Oral Contraceptives and Cigarette Smoking: A Review of the Literature and Future Directions.

INTRODUCTION: Evidence continues to mount indicating that endogenous sex hormones (eg, progesterone and estradiol) play a significant role in smoking-related outcomes. Although approximately one out of four premenopausal smokers use oral contraceptives (OCs), which significantly alter progesterone and estradiol levels, relatively little is known about how OCs may influence smoking-related outcomes. Thus, the goal of this review article is to describe the state of the literature and offer recommendations for future directions. METHODS: In March 2017, we searched seven databases, with a restriction to articles written in English, using the following keywords: nicotine, smoker(s), smoking, tobacco, cigarettes, abstinence, withdrawal, and craving(s). We did not restrict on the publication date, type, or study design. RESULTS: A total of 13 studies were identified. Three studies indicated faster nicotine metabolism in OC users compared to nonusers. Five of six laboratory studies that examined physiological stress response noted heightened response in OC users compared to nonusers. Three studies examined cessation-related symptomatology (eg, craving) with mixed results. One cross-sectional study observed greater odds of current smoking among OC users, and no studies have explored the relationship between OC use and cessation outcomes. CONCLUSIONS: Relatively few studies were identified on the role of OCs in smoking-related outcomes. Future work could explore the relationship between OC use and mood, stress, weight gain, and brain function/connectivity, as well as cessation outcomes. Understanding the role of OC use in these areas may lead to the development of novel smoking cessation interventions for premenopausal women. IMPLICATIONS: This is the first review of the relationship between oral contraceptives (OCs) and smoking-related outcomes. The existing literature suggests that the use of OCs is related to increased nicotine metabolism and physiological stress response. However, the relationship between OC use and smoking-related symptoms (eg, craving) is mixed. Further, no published data were available on OC use and smoking cessation outcomes. Therefore, we recommend additional research be conducted to characterize the relationship between OC use and smoking cessation outcomes, perhaps as a function of the effect of OC use on mood, stress, weight gain, and brain function/connectivity.

Contracepção e desempenho na adolescente atleta / Contraception and performance in teenage athlete

Objetivos: Apresentar os métodos contraceptivos que melhor se adaptam à jovem atleta, correlacionar seus efeitos com possíveis alterações no desempenho atlético ou com os componentes da tríade da atleta (amenorreia, osteoporose e distúrbios alimentares). Método: Foi realizada ampla revisão da literatura, utilizando-se no Medline (PubMed), a estratégia de busca: ("Sports"[Mesh]) AND ("Contraceptive Agents" [Mesh] OR "Contraceptive Agents, Female" [Mesh] AND "Athletic Performance"[Majr])). Foram ainda consultadas as bases: Cochrane Library, SciELO, LILACS e o Google Scholar. Resultados: Somente um de 12 ensaios clínicos para avaliação da relação entre anticoncepção hormonal combinada oral (AHCO) e desempenho atlético sugeriu que o uso do método poderia alterar o desempenho de algumas atletas de elite. O uso contínuo ou estendido da pílula são os preferidos por permitir programar o ciclo menstrual, evitando que sintomas menstruais prejudiquem treinos, competições e viagens, além de prevenir a deficiência de ferro. Conclusões: O AHCO é o método mais usado entre as atletas, sendo o único estudado na literatura para avaliar desempenho atlético. Não foi evidenciada alteração na produção média de energia, composição corporal, frequência cardíaca, pico de captação do oxigênio e glicemia. A escolha do método contraceptivo deve ser sempre individualizada, havendo poucas restrições para adolescentes atletas, permitindo escolha pelo método e regime de administração mais adequado à rotina de vida destas jovens.(AU)

Objective: Introducing the contraceptive methods that are better adapted to the routine and lifestyle of a young athlete and correlate the effects of its use with possible changes in athletic performance or clinical components of the triad (amenorrhea, osteoporosis and eating disorders). Method: An extensive literature review was carried out in national and international digital media. To search in Medline (PubMed), we used the search strategy: (("Sports" [MeSH]) AND ("Contraceptive Agents" [MeSH] OR "Contraceptive Agents, Female" [MeSH] AND "Athletic Performance" [MAJR])). We also consulted SciELO, LILACS and the Google Scholar. Results: Only one study of the 12 clinical trials selected for evaluation of the relationship between oral combined hormonal contraceptives (OCHC) and athletic performance suggested that the use of the method could affect the performance of some elite athletes. The extended-cycle or continuous pill use are mainly preferred for allow programming the menstrual cycle, preventing menstrual symptoms affect training, competitions and travel, and to prevent iron deficiency. Conclusions: The OCHC is the most used method among athletes and it's the only studied in the literature that relates to athletic performance. A change in average production of energy, body composition, heart rate, peak oxygen uptake and glucose was not evidenced. The choice of contraceptive method must be individualized, with few restrictions for teen athletes, allowing the choice of the most appropriate for the routine of life of these young people.(AU)

Sex differences and hormonal influences on response to mechanical pressure pain in humans.

UNLABELLED: Previous studies have demonstrated that sex differences in pain responsivity can be detected using various models of experimentally induced pain. The present study employed the mechanical pressure test in order to examine potential differences in pain report among men, normally menstruating women (NMW), and women taking monophasic oral contraceptives (OCW). Testing occurred during 5 phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) and all participants completed 10 sessions (2 sessions per phase). Menstrual-cycle phase was estimated for OCW based on their first day of menses. Men were tested at time points that roughly corresponded to the intervals during which the different phases occurred in NMW. During the mechanical pressure test, 4 different weights were placed on the fingers, one at a time, and ratings of pain were recorded for 30 seconds. The statistical decision-making model and a forced-choice procedure were used to analyze the response data. Two variables, based on signal detection theory, were thus generated: P(A), a measure of sensory pain, and B, a measure of response bias. P(A) is believed to be a measure of pain sensitivity while B measures stoicism. NMW tended to report lower P(A) values, indicating reduced ability to discriminate among different stimulus intensities, during the menstrual and late luteal phases compared to the luteal phase. OCW reported lower B values, indicating less stoicism, during the menstrual compared to the follicular and ovulatory phases. Men tended to have significantly lower B values than OCW, but not NMW. These results demonstrate subtle menstrual-cycle effects in NMW and OCW. Sex differences were few, with more group differences and trends emerging between OCW and men, as opposed to men and NMW. PERSPECTIVE: The lack of consistent differences between men and NMW underscores the subtle impact of sex and hormonal changes in pain report. In addition, the data obtained in NMW support the notion that changes in hormone levels during the menstrual cycle can lead to changes in pain responsivity as NMW had trends for better discrimination in menstrual phases when estradiol levels were highest.

Effect of oral contraceptive cycle phase on performance in team sport players.

The purpose of this study was to examine whether common team sport performance variables (anaerobic power, reactive strength and repeat sprint ability) are affected by acute hormonal fluctuation within a monophasic oral contraceptive (OC) cycle. Ten female team sport athletes completed performance tests at three time points of a single OC cycle, during the consumption phase (CONS), early (WITH1) and late in the withdrawal phase (WITH2). Tests included drop jumps (30cm and 45cm heights), a counter movement jump, a 10s cycle sprint test and a 5x 6s repeated sprint cycle test. Resting endogenous serum oestradiol and progesterone concentrations were also measured. No significant differences were observed between phases for the counter movement jump and cycle tests (total work and peak power). Reactive strength measured from the 30cm drop height was significantly lower during WITH2 (162+/-38cms(-1)) compared to both CONS (177+/-44cms(-1)) and WITH1 (178+/-40cms(-1)) (p<0.05). Reactive strength measured from the 45cm drop height was significantly higher in CONS (178+/-48cms(-1)) compared to both WITH1 and WITH2 (161+/-39cms(-1) and 158+/-29cms(-1), respectively) (p<0.05). Serum oestradiol levels were greater during WITH2 compared to both WITH1 and CONS (p<0.05) but there was no difference in serum progesterone levels. The results demonstrate that for female team sport athletes, only reactive strength varied significantly throughout an OC cycle, possibly due to the action of hormones on neuromuscular timing and the stretch-shortening cycle.

Circulating alpha1-antitrypsin in the general population: determinants and association with lung function.

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. METHODS: In 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels < or = 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. RESULTS: Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p < 0.001), that disappeared after adjustment for CRP (p = 0.28). In addition, the AAT and FEV1 association was modified by gender, menopausal status in women, and smoking. CONCLUSION: The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.

Clinically relevant drug interactions with antiepileptic drugs.

Some patients with difficult-to-treat epilepsy benefit from combination therapy with two or more antiepileptic drugs (AEDs). Additionally, virtually all epilepsy patients will receive, at some time in their lives, other medications for the management of associated conditions. In these situations, clinically important drug interactions may occur. Carbamazepine, phenytoin, phenobarbital and primidone induce many cytochrome P450 (CYP) and glucuronyl transferase (GT) enzymes, and can reduce drastically the serum concentration of associated drugs which are substrates of the same enzymes. Examples of agents whose serum levels are decreased markedly by enzyme-inducing AEDs, include lamotrigine, tiagabine, several steroidal drugs, cyclosporin A, oral anticoagulants and many cardiovascular, antineoplastic and psychotropic drugs. Valproic acid is not enzyme inducer, but it may cause clinically relevant drug interactions by inhibiting the metabolism of selected substrates, most notably phenobarbital and lamotrigine. Compared with older generation agents, most of the recently developed AEDs are less likely to induce or inhibit the activity of CYP or GT enzymes. However, they may be a target for metabolically mediated drug interactions, and oxcarbazepine, lamotrigine, felbamate and, at high dosages, topiramate may stimulate the metabolism of oral contraceptive steroids. Levetiracetam, gabapentin and pregabalin have not been reported to cause or be a target for clinically relevant pharmacokinetic drug interactions. Pharmacodynamic interactions involving AEDs have not been well characterized, but their understanding is important for a more rational approach to combination therapy. In particular, neurotoxic effects appear to be more likely with coprescription of AEDs sharing the same primary mechanism of action.

Comparison of plasma and urinary levels of 2-hydroxyestrogen and 16 alpha-hydroxyestrogen metabolites.

A modified ELISA assay for measurement of the two estrogen metabolites 2-hydroxyestrone (2OHE1) and 16alpha-hydroxyestrone (16alphaOHE1) in plasma and serum has been developed. Previously, these have only been measured in urine. It is not known how well the measurements of these metabolites in urine and plasma are correlated. The goal of this study was to compare urinary and plasma levels of 2OHE1 and 16alphaOHE1 and their ratios and to explore how they were affected by ethnicity, dietary and genetic factors, and medication use. Blood and urine samples were obtained from 511 nulliparous women, aged 17-35, from four ethnic groups during the same visit at the study center, on a random day of the menstrual cycle. The overall correlation between the 2OHE1/16alphaOHE1 ratio in plasma and urine was fair (rs = 0.52; p < 0.0001). In general, the correlation between the 2OHE1/16alphaOHE1 ratio in urine and plasma was higher among women not using oral contraceptives (OCs) (rs = 0.58; p < 0.0001) than among women currently using OCs (rs = 0.34; p < 0.0001). The correlation was highest for samples obtained during the mid-cycle in among non-OC users (rs = 0.83; p < 0.0001). Among non-OC users, the urinary 2OHE1/16alphaOHE1 ratio was stable over the menstrual cycle while there was an increase in the plasma 2OHE1/16alphaOHE1 ratio. The strongest factors predicting discordance between the urinary and plasma 2OHE1/16alphaOHE1 ratios among non-OC users were a baseline urinary 2OHE1/16alphaOHE1 ratio in the three upper quartiles (p < 0.001), the menstrual cycle phase (p = 0.001), and the number of cups of coffee consumed per day (p = 0.006). Among current OC users, the strongest predictors of discordance between the urinary and plasma 2OHE1/16alphaOHE1 ratios were a baseline urinary 2OHE1/16alphaOHE1 ratio in the three lower quartiles (p < 0.001), being black (p = 0.001), and being Asian (p = 0.014). In conclusion, we found that the correlation between the two methods was fair and varied according to the baseline urinary 2OHE1/16alphaOHE1 ratio, ethnic group, OC status, coffee consumption, and time of menstrual cycle when the samples were obtained.

Oral contraceptives as substrates and inhibitors for human cytosolic SULTs.

Cytosolic sulfotransferases (SULTs) in mammals are involved in the biotransformation and homeostasis of various endogenous and xenobiotic compounds. The current study aimed to examine the sulfation of contraceptive compounds by various human cytosolic SULTs and to investigate the inhibitory effects and mode of action of these compounds on the sulfation of 17beta-estradiol, a major endogenous estrogen. A systematic study using all eleven known human cytosolic SULTs revealed the differential substrate specificity of these enzymes for the eight representative contraceptive compounds and two endogenous estrogens (estrone and 17beta-estradiol) tested as substrates. Activity data showed that SULT1A1 displayed the strongest activity toward 17alpha-ethynylestradiol. Kinetic studies revealed that the V (max) value of the sulfation of 17alpha-ethynylestradiol by SULT1A1 was 1.64 times that of the sulfation of 17beta-estradiol, while the K (m) values were almost equal for the two compounds. The inhibitory effects of three contraceptive compounds on the sulfation of 17beta-estradiol by SULT1A1 were examined. IC(50) values determined were 0.193, 1.84, and 2.98 mM, respectively, for 19-norethindrone acetate, ethynodiol diacetate and mifepristone. Kinetic analyses indicated that the mechanism underlying the inhibition by these contraceptives is of a mixed noncompetitive type. Metabolic labeling experiments confirmed the sulfation of contraceptive compounds and the release of their sulfated derivatives by HepG2 human hepatoma cells. Collectively, the results obtained suggest a role of sulfation in the metabolism of contraceptive compounds in vivo. Moreover, in view of their inhibitory effects on the sulfation of 17beta-estradiol, these compounds may potentially act to disrupt the homeostasis of endogenous estrogens.

The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro.

Dienogest is a synthetic steroid that has been used as a progestogen in contraceptive pills and is currently being studied for its possible clinical use in the treatment of endometriosis. In this study, we investigated the direct effects of dienogest in differentiation and proliferation of human endometrial stromal cells (ESC) in vitro. After 12 days in the presence of oestradiol (10(-8) mol/l) plus dienogest (10(-6) mol/l), cultured ESC underwent morphological differentiation and produced prolactin, a typical marker for decidualization. By using Northern blot analysis and radioimmunoassay, it was shown that treatment of ESC with oestradiol (10(-8) mol/l) plus dienogest (10(-9) to10(-6) mol/l) led to an increase in the levels of prolactin mRNA and prolactin production in a dose-dependent manner. Additionally, RU-486, a progesterone receptor antagonist, almost completely inhibited dienogest-induced prolactin production. As shown by the thymidine uptake method, there was a dose-dependent inhibition of ESC proliferation with dienogest (P < 0.01, control versus concentrations >10(-7) mol/l). The significant inhibition of ESC proliferation by dienogest (10(-7) mol/l) was partially reversed by RU-486 (10(-6) mol/l). In summary, dienogest directly acts on endometrial tissue in progestogenic response, such as decidualization, increased prolactin production and growth retardation. These data imply that dienogest exerts direct effect in suppressing growth of endometriotic implants.

Interactions between oral contraceptives and antifungals/antibacterials. Is contraceptive failure the result?

The effectiveness of oral contraceptives may be impaired by concomitant treatment with antimicrobials. This may occur because of reductions in plasma concentrations of ethinylestradiol by the induction of hepatic metabolism, as for rifampicin (rifampin) and possibly griseofulvin, or in a small percentage of women because of interference with enterohepatic recirculation. There are no scientific data to support the anecdotal evidence that the concomitant use of combined oral contraceptives and antimicrobials reduces contraceptive efficacy in the majority of women. It has been postulated that there is a subset of women in whom the enterohepatic recirculation of ethinylestradiol plays an important role. In these women the action of an antimicrobial may reduce the efficacy of oral contraceptives by interfering with this mechanism. Studies that have quantitatively examined these effects may have failed to include women from this subset because of the small numbers involved in the studies. On the other hand, there are no good prospective studies comparing contraceptive failure rates between compliant women who use combined oral contraceptives with and without antimicrobials. All women using combined oral contraceptives should be informed of the very low level of risk of interactions with antimicrobials (probably about 1%) and that it is not possible to identify who may be at risk. Women concerned about this low level of risk should be given information about the use of barrier methods or avoidance of intercourse during the first 7 days of concomitant antimicrobial therapy and for 7 subsequent days. Women who have had previous contraceptive failures or developed breakthrough bleeding during concomitant antimicrobial use should be strongly advised to follow these precautions, as they may be part of the subset of women at higher risk of contraceptive failure.

Oral contraceptive therapy in women: drug interactions and unwanted outcomes.

Oral contraceptives are highly effective contraceptive agents used worldwide that have a relatively low incidence of adverse side effects. Drug interactions that decrease the efficacy of contraception or that limit the efficacy of concomitant medications can occur. The most frequent clinically encountered interactions involve antibiotics or anticonvulsants. The incidence of adverse thrombotic events is low and can be further minimized by the use of low estrogen doses; avoidance of smoking or not prescribing oral contraceptives in smokers; and avoidance of exposure in genotypes at high risk for thrombosis (Leiden Factor V mutation).

Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid.

Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly, we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (> or = 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (> or = 0.01 mg/kg). Also, it was slightly uterotrophic (> or = 1 mg/kg) with very low binding affinity for oestrogen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

Characterization of the novel progestin gestodene by receptor binding studies and transactivation assays.

Gestodene is a novel progestin used in oral contraceptives with an increased separation of progestogenic versus androgenic activity and a distinct antimineralocorticoid activity. This specific pharmacological profile of gestodene is defined by its pattern of binding affinities to a variety of steroid hormone receptors. In the present study the affinity of gestodene to the progesterone receptor (PR), the androgen receptor (AR), the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR) and the estrogen receptor (ER) was re-evaluated by steroid binding assays and compared to those obtained for 3-keto-desogestrel and progesterone. The two synthetic progestins displayed identical high affinity to rabbit PR and similar marked binding to rat AR and GR, while progesterone showed high affinity to PR but only low binding to AR and GR. Furthermore, 3-keto-desogestrel exhibited almost no binding to MR, whereas gestodene, similar to progesterone, showed marked affinity to this receptor. In addition to receptor binding studies, transactivation assays were carried out to investigate the effects of gestodene on AR-, GR- and MR-mediated induction of transcription. In contrast to progesterone, which showed antiandrogenic activity, gestodene and 3-keto-desogestrel both exhibited androgenic activity. Furthermore, all three progestins exhibited weak GR-mediated antagonistic activity. In contrast to progesterone, which showed almost no glucocorticoid activity, gestodene and 3-keto-desogestrel showed weak glucocorticoid action. In addition, gestodene inhibited the aldosterone-induced reporter gene transcription, similar to progesterone, whereas unlike progesterone, gestodene did not induce reporter gene transcription. 3-Keto-desogestrel showed neither antimineralocorticoid nor mineralocorticoid action.

Interactions between clinically used drugs and oral contraceptives.

Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin).

Anticoncepcionais orais e cancer de mama / Oral contraceptives and breast cancer

A relacao entre o uso anticoncepcionais orais (ACO) e cancer de mama e discutida com base em analise critica dos trabalhos publicados na literatura. Sao analisados parametros gerais e aspectos referentes ao uso de ACO, como idade de inicio, duracao, relacao com a primeira gestacao de termo, diferentes formulacoes e gravidade do cancer nas usuarias. Pode-se concluir que o risco de cancer de mama nao e significativamente elevado em usuarias adultas, mas aumentando em adolescentes e que estas, quando desenvolvem cancer de mama, podem apresentar formas de pior prognostico. Nao esta definida a influencia dos outros parametros estudados, mas provavelmente quanto mais precoce e mais prolongado for o uso de ACO, maior sera o risco de cancer de mama.

Estudo clínico multicêntrico sobre o efeito metabólico do contraceptivo mensal injetável contendo acetofenido de dihidroxiprogesterona 150 mg + enantato de estradiol 10 mg / A multicenter clinical trial on the metabolic effect of an injectable monthly contraceptive containing dihydroxyprogesterone acetophenide 150 mg + estradiol enanthate 10 mg

O efeito metabólico do contraceptivo mensal injetável contendo acetofenido de dihidroxiprogesterona (DHPA) 150 mg + enantato de estradiol (Een) 10 mg foi comparado ao de outros métodos anticoncepcionais comumente utilizados (pílulas contendo: etinilestradiol (EEn) 0,050 mg + levonogestrel (LNG) 0,250 mg, EE 0,030 + LNG 0,150 mg; e EE 0,030/0,040/0,030mmg + LNG 0,050/0,075/0,0125 mg; enantato de noretisterona (NEE) 200 mg via i.m.; e métodos nao-hormonais. Foram determinados os triglicerídeos séricos, colesterol HDL/LDL, cobre, ceruloplasmina, cortisol total e livre, CBG e testosterona total e livre e SHBG de usu rios crônicas. Este estudo contou com a participaçäo do total de 237 mulheres. As usuárias de métodos nao-hormonais utilizadas como controle apresentaram níveis mais altos de triglicerídeos. Os níveis de testosterona total e livre foram mais baixos em mulheres que utilizavam DHPA 150 mg + Een 10 mg e nas que tomavam pílulas anticoncepcionais (p<0,05 - 0,01). Tais alteraçöes foram levemente menores no grupo que utilizou o injetável. Os efeitos do DHPA 150 mg + EEn 10 mg sobre o colesterol HDL/LDL, cobre, ceruloplasmina, CBG, cortisol total e livre e SHBG foram raros ou inexistentes. Entretanto, com as pílulas anticoncepcionais (mesmo as de formulaçäo de baixa dosagem) ocorreram alteraçöes em todas essas vari eis, que foram altamente significativas na comparaçäo com o método injetável (p< 0,01) e com os métodos nao-hormonais (p<0,01); näo houve diferenças entre estes dois últimos métodos. Os resultados sugerem que o efeito metabólico da injeçäo mensal i.m. de DHPA 150 mg + Een 10 mg näo é superior aos dos anticoncepcionais orais comumente utilizados. Estes resultados também nao sugerem que a dose contida nesse injetável seja excessiva. Nao há qualquer evidência de que ele produza efeito cumulativo no organismo. Esses achados devem ser levados em consideraçäo com relaçäo à segurança do uso a longo prazo desse injetável.