Effects of an extended flexible regimen of an oral contraceptive pill containing 20 µg ethinylestradiol and 3 mg drospirenone on menstrual-related symptoms: a randomised controlled trial.

OBJECTIVES: The aim of the study was to assess the efficacy for menstrual-related symptoms of an extended flexible regimen of an oral contraceptive pill containing 20 µg ethinylestradiol and 3 mg drospirenone in comparison with a 24/4 d cyclical regimen of the same formulation. METHODS: This randomised, non-inferiority, open-label, multicentre study was conducted in women aged 18-39 years. Their menstrual-related symptoms were assessed using the Penn Daily Symptom Rating (DSR17). Participants were randomised to use an extended flexible regimen of 20 µg ethinylestradiol and 3 mg drospirenone (EE/DRSPe.flex), comprising 168 consecutive days with a 4-d hormone-free interval (HFI, allowing for management of unexpected bleeding) or a conventional 24/4 cyclical regimen of the same pill (EE/DRSP24/4). The primary measure of efficacy was the percentage change in DSR17 total score from baseline to cycle 6. The secondary measures of efficacy were the percentage changes in DSR17 total score from baseline after each 28-d interval throughout the entire study and in the scores for individual DSR17 symptoms. RESULTS: The primary analysis demonstrated that EE/DRSPe.flex was not inferior to EE/DRSP24/4 (Mean DSR17 score 9.1; 95% confidence interval (CI) - 2.5, 20.6; p = 0.123). Analysis at intervals throughout the entire evaluation period showed greater reduction in DSR17 total score for EE/DRSPe.flex than for the 24/4 regimen (p < 0.001). The decreases in individual scores for the symptoms 'poor coordination' and 'depression/feeling sad/down or blue' were greater for the extended flexible regimen than for the cyclical regimen (p < 0.05). CONCLUSION: The extended flexible regimen was not inferior to the 24/4 cyclical regimen in terms of the primary endpoint. It significantly improved symptoms in the interval analysis, and the effects on specific DSR17 symptoms, compared with the cyclical regimen.

Activation of NF-kappaB and COX-2 expression is associated with breakthrough bleeding in patients using oral contraceptives in extended regimens.

The objective of the present study was to determine whether there is an increase in endometrial inflammation associated with the occurrence of breakthrough bleeding in patients using an oral contraceptive in extended regimens. The presence of nuclear factor NF-kappaB and Cox-2 expression was determined by immunohistochemistry in endometrial samples removed by hysteroscopy from patients with breakthrough bleeding during continuous use of an oral contraceptive containing gestodene. All patients had a history of menorrhagia associated or not with the presence of uterine pathology. The percentage of endometria showing a positive staining reaction for NF-kappaB in cell nuclei was significantly higher in patients with breakthrough bleeding than in those with amenorrhea. Cox-2 expression in the endometrium was also significantly more frequent in patients with breakthrough bleeding. The occurrence of breakthrough bleeding in patients with uterine pathology using combined oral contraceptives is associated with the activation of endometrial inflammation through the NF-kappaB pathway.

The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium.

OBJECTIVE: To study Cox-2 expression in relation to bleeding patterns in patients using an oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinylestradiol (DRSP/EE). METHODS: Forty-three patients of reproductive age with symptoms of menorrhagia and dysmenorrhoea, who were submitted to endometrial resection, were enrolled. Twelve patients were in the proliferative phase and the remaining 31 were either currently using DRSP/EE or had discontinued its use four to eight days prior to hysteroscopy. Cox-2 and Ki-67 expression were determined in the endometrium using immunohistochemistry. RESULTS: Cox-2 expression was significantly inhibited in the glandular epithelium of patients who became amenorrhoeic during DRSP/EE use; however, in patients with breakthrough bleeding and in those who had stopped oral contraceptive use, a significant increase occurred in Cox-2 expression in the endometrium. Ki-67 expression decreased significantly during DRSP/EE use, but returned to proliferative phase values four to eight days after discontinuation of treatment. CONCLUSION: These results suggest that endometrial bleeding during DRSP/EE use is associated with an increase in Cox-2 expression in the endometrium. A similar increase was also seen four to eight days following discontinuation of the oral contraceptive.

Is aromatase expression in the endometrium the cause of endometriosis and related infertility?

Aromatase expression in the endometrium seems to play a pivotal role in the development of endometriotic lesions. Because inflammatory mediators such as prostaglandin E2 appear to activate aromatase in the cells of the endometrial stroma, it was hypothesised that the ensuing inflammation caused by the arrival of aromatase-positive cells in the peritoneal cavity would stimulate local estrogen production, which would in turn facilitate the development of endometriotic lesions by suppressing macrophage phagocytosis. Aromatase expression in the eutopic endometrium will also hamper ovum nidation, thus causing infertility. Progestins, such as gestodene and danazol, are potent inhibitors of aromatase expression in the endometrium, and the use of vaginal rings with danazol in doses that do not block ovulation is associated with the occurrence of pregnancy in patients with severe endometriosis without the need for surgery. A local effect on the endometrium suppressing aromatase expression has been suggested as a possible mechanism of action for the danazol ring.

Testosterone replacement therapy in the climacteric: benefits beyond sexuality.

Testosterone therapy during menopause has a wide range of benefits that reach beyond the realm of human sexuality. This is a consequence not only of the widespread distribution of androgen receptors in various extragonadal tissues but also of the conversion of androgens to estrogens in the tissues in which aromatase expression is present. For this reason, testosterone therapy during the climacteric years will not only supply androgens but will also stimulate estrogen production in tissues that express aromatase. Furthermore, the bioavailability of androgens to the tissues depends not only on the rate of their production by the postmenopausal ovaries and adrenals but also on the circulating levels of sex hormone-binding globulin (SHBG). Tibolone inhibits SHBG production in the liver, thus increasing free testosterone levels. The association of tibolone with testosterone as a form of androgen replacement therapy during the climacteric is discussed, as is the use of low-dose testosterone, tibolone or the association of both in perimenopausal patients with signs of androgen deficiency. Testosterone treatment has a boosting effect not only on human sexuality but also on the sensation of well-being, a stimulatory effect conferred by the increase in beta-endorphins.

Fatores associados a qualidade de vida no trabalho de profissionais da saúde da atenção primária à saúde / Factors associated with the quality of life at work of health professionals in primary health care / Factores asociados a la calidad de vida en el trabajo de los profesionales de la salud en la atención primaria de salud

Objetivo: analisar os principais fatores que estão associados a qualidade de vida no trabalho de profissionais da saúde da atenção primária à saúde. Método: Estudo transversal de abordagem quantitativa, realizada com 163 trabalhadores, os quais respon- deram ao questionário Total Quality of Work Life-42 e a um outro sobre características sociodemográficas e laborais. Resultados: Dos respondentes 84% sexo feminino; 47,9% pardos; 55,2% casados; 55,8% com grau de escolaridade médio, 23,9% graduados e 15,5% possuíam pós-graduação. A renda foi observada correlação positiva entre renda e qualidade de vida, além de fatores pessoais como ser do sexo masculino, solteiro, tempo de trabalho no município (anos). Verificou-se que profissionais do sexo feminino apre- sentaram menores escores de qualidade de vida no aspecto econômico e político quando comparados aos do sexo masculino. Conclusão: Medidas devem ser tomadas para pro- mover um ambiente laboral que mantenha a qualidade de vida no trabalho e, por sua vez, favorecer a saúde física e mental dos profissionais de atenção primária à saúde.

Objective: to analyze the main factors that are associated with the quality of life at work of health professionals in primary health care. Method: Cross-sectional study with a quantitative approach, carried out with 163 workers, who answered the Total Quality of Work Life-42 questionnaire and another on sociodemographic and labor characteristics. Results: Of the respondents, 84% were female; 47.9% brown; 55.2% married; 55.8% had a high school education, 23.9% graduated and 15.5% had a postgraduate degree. Income was observed to have a positive correlation between income and quality of life, in addition to personal factors such as being male, single, working time in the municipality (years). It was found that female professionals had lower quality of life scores in the economic and political aspects when compared to males. Conclusion: Measures must be taken to promote a work environment that maintains the quality of life at work and, in turn, favors the physical and mental health of primary health care professionals.

Objetivo: analizar los principales factores que se asocian a la calidad de vida en el trabajo de los profesionales de la salud en la atención primaria de salud. Método: Estudio transversal con enfoque cuantitativo, realizado con 163 trabajadores, quienes respondieron el cuestionario de Total Quality of Work Life-42 y otro sobre características sociodemográficas y laborales. Resultados: De los encuestados, el 84% eran mujeres; 47,9% marrón; 55,2% casados; El 55,8% tenía educación secundaria, el 23,9% se graduó y el 15,5% tenía posgrado. Ingreso, se observó una correlación positiva entre ingreso y calidad de vida, además de factores personales como ser hombre, soltero, tiempo de trabajo en la ciudad (años). Se constató que las mujeres profesionales tenían puntajes de calidad de vida más bajos en los aspectos económico y político en comparación con los hombres. Conclusión: Se deben tomar medidas para promover un ambiente de trabajo que mantenga la calidad de vida en el trabajo y, a su vez, favorezca la salud física y mental de los profesionales de la atención primaria de salud.

Clinical guidelines for improving compliance with hormone therapy in Latin American women during the menopausal transition and thereafter.

OBJECTIVE: To provide uniform, objective guidance for physicians and other health care workers in Latin America to enhance compliance with hormone therapy (HT), and to provide a tool for continued medical education and a source for answering clinical questions. METHOD: Literature search using MEDLINE; identification of key relevant publications by a five-member expert committee; creation and validation of a 60-item questionnaire used to survey the opinion of 72 physicians participating in a Latin American symposium, "The Faces of Menopause". RESULTS: On the basis of the validated responses, major points were identified to enhance compliance with HT with specific reference to Latin America, and two algorithms were created to provide practical guidance. CONCLUSION: The present guidelines will facilitate optimal compliance with therapy in Latin American postmenopausal women who opt for HT and for whom HT is indicated.

Latin American position on the current status of hormone therapy during the menopausal transition and thereafter.

OBJECTIVE: Data from placebo-controlled, randomized clinical trials conducted during the past few years resulted in critical re-evaluation of the overall health benefits of hormone therapy (HT) in women during the menopausal transition and thereafter. These data stimulated vigorous debate among experts and produced several position papers by North American and European authorities providing guidance on the use of HT. It is well known that cultural, geographic and ethnic differences influence the acceptance and risk perception of HT. Therefore, it was considered essential to present a position specifically relevant to Latin American countries. METHODS: A Latin American Expert Panel, convening in Salvador, Bahia, Brazil, obtained consensus on recommendations for HT that incorporated the findings of the most recently published reports. The panelists' opinions were surveyed by means of the Likert scale along five categories ranging from complete agreement to complete disagreement. RESULTS: The Panel presented 13 recommendations and considered three additional issues relevant to HT use. There was consensus that HT during the perimenopause and thereafter is warranted in Latin American women in particular for the management of vasomotor symptoms. HT may also be an option for osteoporosis prevention in women at significant risk, after evaluation of risks/benefits and after consideration of alternative therapies. HT should be individualized and prescribed at the lowest effective dose. CONCLUSIONS: The Panel concluded that HT remains a safe and effective treatment option for peri- and postmenopausal Latin American women.

Effects of a single Silastic contraceptive implant containing nomegestrol acetate (Uniplant) on endometrial morphology and ovarian function for 1 year.

PURPOSE: This study was undertaken to evaluate the effects of a subdermal implant containing nomegestrol acetate (Uniplant) on endometrial histology and ovarian function. METHODS: Twenty healthy female volunteers of reproductive age were included and completed a menstrual diary throughout the study. Hysteroscopy, transvaginal sonography and blood sampling were performed prior to implant insertion (control cycle) and following 6 and 12 months of Uniplant use. Transvaginal sonography was performed every other day from Day 8 of the cycle up to the obtainment of sonographic evidence of a 12-mm follicle, then every day until the obtainment of sonographic evidence of follicular rupture and thereafter every other day until the next menstrual bleeding. Blood samples were taken for the measurement of estradiol, follicle-stimulating hormone, luteinizing hormone and progesterone on the same days on which transvaginal sonography was performed. The implants were removed after 1 year. RESULTS: Twenty percent of cycles were ovulatory, and 80% were anovulatory. The development of persistent nonluteinized follicle occurred in 40% of all cycles studied, inadequate luteal phase occurred in 20% of cycles and no follicular development occurred in 40%. Endometrial thickness remained below 8 mm in all cycles studied. Alterations in endometrial vascularization were observed in all treated cycles. CONCLUSION: Our results suggest that this long-acting contraceptive method affects follicular growth and endometrial vascularization, disrupts endometrial architecture and leads to inadequate luteal phase.

[Number, shape, and topography of leakage points in patients with central serous chorioretinopathy]. / Número, tipo e topografia dos pontos de vazamento em pacientes com coriorretinopatia serosa central.

PURPOSE: To evaluate the number, shape and topography of leakage points in patients with central serous chorioretinopathy (CSC). METHODS: Digital photographic files of fluorescein angiography with the diagnosis of CSC were reviewed by the author. The cases considered in remission and the examinations related to the same episode were excluded. The author filled out a form containing medical record number, initials, sex, age, date of the examination and leakage point characteristics (number, shape, and topography) of the selected cases. RESULTS: The examinations of 418 patients (455 eyes) were included, with a male:female ratio of 2.32:1. Ninety-one point fifteen percent of the patients presented the disease unilaterally and 8.85% bilaterally. The mean age was 43.04 years (range, 19-68 years). Among the 455 selected eyes, 88.35% presented typical forms of CSC while 10.11% decompensation of the retinal pigment epithelium and 1.54% with isolated retinal pigment epithelium (RPE) detachment. The evaluation of typical forms of CSC showed a leakage point with uniform dye spread (inkblot) in 88.81% and 11.19% with a smoke-stack phenomenon. Regarding the leakage points, 46.01% were located in the upper nasal quadrant, 23.27% in the upper temporal quadrant, 19.18% in the lower nasal quadrant, 11.01% in the lower temporal quadrant and 0.53% in the subfoveal area. CONCLUSIONS: In our series men were affected approximately two times more often then women, most of them with a unilateral involvement and in around the fourth decade of life. About 90% of the patients presented the typical forms, with 1 or 2 inkblot points or leakage. The superior nasal quadrant was the most affected. The isolated RPE detachment rarely occurred. Decompensation of RPE affected about 10% of the patients.

[Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in central serous chorioretinopathy: case report]. / Terapia fotodinâmica com verteporfirina em neovascularização coroidiana subfoveal secundária a coriorretinopatia serosa central: relato de caso.

We report the use of photodynamic therapy with verteporfin for subfoveal choroidal neovacularization in central serous chorioretinopathy. Visual acuity improved (0.5 to 1.0) 30 days after the first session. After 141 days, the choroidal neovascularization reactivated and the patient was retreated. Again, visual acuity improved (0.5 to 1.0) 30 days afterwards. It remains stable after 20 months. Photodynamic therapy can be efficient in the treatment of choroidal neovascularization in central serous chorioretinopathy.

c-erbB2 over-expression in endometrial hyperplasia induced by estrogens.

OBJECTIVE: To determine whether the presence of c-erbB2 expression in both spontaneous and estrogen-induced hyperplasia can affect the number of Ki-67-positive cells. PATIENTS AND METHODS: Thirty-two postmenopausal women with endometrial hyperplasia occurring spontaneously or after using unopposed estrogens were studied. The number of cells undergoing mitosis was estimated by immunohistochemical detection of the Ki-67 antigen and compared with the presence or absence of c-erbB2 over-expression. RESULTS: The percentage of cell nuclei showing positivity for Ki-67 was significantly higher in cases of endometrial hyperplasia that displayed c-erbB2 over-expression when compared to negative cases. CONCLUSION: The presence of c-erbB2 over-expression in endometrial hyperplasia is associated with a higher number of cells being positive for the Ki-67 proliferation marker.

P53 expression in spontaneous and estradiol-induced endometrial hyperplasia during menopause.

OBJECTIVE: To determine the percentage of endometrial hyperplasia positive for p53 expression in both spontaneously occurring cases or following the use of unopposed estradiol. METHODS: Fifty-four postmenopausal patients with endometrial hyperplasia diagnosed by endometrial biopsy and hysteroscopy were recruited to this study. Thirty-three patients had used unopposed estradiol for periods of time from 1 to 3 years. P53 expression was detected in paraffin-embedded endometrial specimens by immunohistochemical methods. RESULTS: The percentage of endometrial hyperplasia positive for p53 expression was significantly greater in spontaneously occurring hyperplasia than in cases induced by the unopposed use of estradiol. CONCLUSION: Endometrial hyperplasia caused by the unopposed use of estradiol during menopause probably harbors fewer genomic errors than those cases occurring spontaneously.

Detection of endometrial intraepithelial neoplasia (EIN) in postmenopausal endometrium.

OBJECTIVES: To detect the presence of endometrial intraepithelial neoplasia (EIN) in the endometrium of postmenopausal patients. PATIENTS AND METHODS: Sixty-three postmenopausal patients with endometrial polyps (n=48), hyperplasia (n=12) and endometrioid carcinoma (n=3) were enrolled for this study. The diagnosis of EIN was made by using morphological criteria and immunohistochemical methods for detection of PTEN and bcl-2. RESULTS: EIN lesions were found in cases of endometrial polyp (n=1), atrophic endometrium (n=1) and in hyperplasia (n=1). The glands were packed, showed cytological atypia and were negative for both PTEN and bcl-2. Three patients with endometrial hyperplasia had isolated PTEN-negative glands but they were still bcl-2 positive. CONCLUSIONS: The use of immunohistochemical methods helps detect the presence of EIN in the postmenopausal endometrium but does not substitute the morphological criteria for this diagnosis.

The effect of pycnogenol on patients with dysmenorrhea using low-dose oral contraceptives.

OBJECTIVE: Menstrual symptoms such as dysmenorrhea usually occur during the hormone-free interval in oral contraceptive users. Progestin withdrawal activates NF-κB transcription factor, which upregulates both vascular endothelial growth factor (VEGF) and Cox-2 expression in the endometrium. The use of natural NF-κB inhibitors such as pycnogenol may block this response, improving dysmenorrhea. PATIENTS AND METHODS: Twenty-four patients with severe dysmenorrhea were allocated to one of two treatment groups. In Group A (n=13), women were treated with an oral contraceptive containing 15 µg of ethinyl estradiol and 60 mg of gestodene (Adoless(®)) in a 24/4 regimen for three consecutive cycles. Women in Group B (n=11) used the same contraceptive regimen together with 100 mg of pycnogenol (Flebon(®)) continuously for 3 months. Pain scores were graded using a visual analog scale (VAS) before and during the hormone-free interval at the end of the third treatment cycle. RESULTS: Before treatment, VAS pain scores for dysmenorrhea were 8 and 9 in Groups A and B, respectively. However, by the end of the third treatment cycle, pain scores had decreased significantly (P<0.05) both in groups A and B. The final pain scores were 6 in Group A and 2 in Group B, a difference that was statistically significant (P<0.0001). In Group B, 27% of the patients became pain-free, while in Group A, none of the women reported complete disappearance of this symptom. The number of bleeding days was also lower in Group B. DISCUSSION: Pycnogenol effectively decreased pain scores and the number of bleeding days when administered concomitantly with a low-dose 24/4 oral contraceptive containing gestodene.

Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain.

Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain.

The effect of oral contraceptives on aromatase and Cox-2 expression in the endometrium of patients with idiopathic menorrhagia or adenomyosis.

BACKGROUND: The presence of aromatase and cyclooxygenase-2 (Cox-2) expression was investigated in the endometrium of patients with idiopathic menorrhagia or adenomyosis. The effect of oral contraceptives administered in extended regimens on the endometrial expression of these enzymes was also investigated. METHODS AND RESULTS: Aromatase expression was detected by immunohistochemistry in the endometrial glands and stroma of patients with idiopathic menorrhagia or adenomyosis. There was no difference in the percentage of aromatase expression in the endometria between the two groups. The mean intensity of Cox-2 expression in the glandular epithelium also did not differ significantly between the groups. Among the patients using oral contraceptives in extended regimens, the relative decrease in both aromatase and Cox-2 expression was significantly greater in amenorrheic patients compared with those who were experiencing breakthrough bleeding. CONCLUSION: The presence of aromatase expression in the endometrium is associated with the occurrence of menorrhagia, irrespective of the presence of adenomyosis. Continuous expression of these enzymes in the endometrium of users of oral contraceptives in extended regimens is positively associated with the presence of breakthrough bleeding. This suggests a role for both aromatase and Cox-2 in the etiology of abnormal uterine bleeding.

Correlation between aromatase expression in the eutopic endometrium of symptomatic patients and the presence of endometriosis.

OBJECTIVE: To investigate whether aromatase expression in the eutopic endometrium correlates with the presence and severity of endometriosis in patients with infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy. PATIENTS: The study involved 106 patients of reproductive age with symptoms of dysmenorrhea and infertility. Sixteen endometriosis-free asymptomatic patients were used as a control group. METHODS: Concomitant laparoscopy and hysteroscopy was carried out in all cases. An endometrial biopsy was taken to determine aromatase p450 expression by immunohistochemistry. Endometriosis was staged according to the American Society of Reproductive Medicine classification. RESULTS: Endometriosis was diagnosed by laparoscopy in 92/106 symptomatic patients. In this group, aromatase expression was detected in the eutopic endometrium of 66/92 patients with endometriosis (72%) and in 13/14 (95%) patients in the symptomatic, endometriosis-free group (P = 0.09). Aromatase expression was not detected in any patients from the control group. In the endometriosis group, aromatase expression was detected in the eutopic endometrium of 28/45 patients (62%) with American Society of Reproductive Medicine classification stage 1 of the disease, in 11/14 patients (78%) with stage II, 14/20 patients (70%) with stage III, and in 12/13 patients (92%) with stage IV; however, the difference was only statistically significant between stages I and IV (P = 0.04). CONCLUSION: Aromatase expression in the endometrium was associated with the presence of dysmenorrhea and infertility irrespective of the presence of endometriosis. When endometriosis was present, however, there was a tendency for aromatase expression to be positively correlated with dysmenorrhea severity.

Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain.

BACKGROUND: The effect of resveratrol on the management of endometriosis-related pain was investigated in 12 patients who failed to obtain pain relief during use of an oral contraceptive containing drospirenone + ethinylestradiol. METHODS AND RESULTS: The addition of 30 mg of resveratrol to the contraceptive regimen resulted in a significant reduction in pain scores, with 82% of patients reporting complete resolution of dysmenorrhea and pelvic pain after 2 months of use. In a separate experiment, aromatase and cyclo-oxygenase-2 expression were investigated in the endometrial tissue of 42 patients submitted to laparoscopy and hysteroscopy for the management of endometriosis. Sixteen of these patients were using oral contraceptives alone prior to hospital admission, while the remaining 26 were using them in combination with resveratrol. Inhibition of both aromatase and cyclo-oxygenase-2 expression was significantly greater in the eutopic endometrium of patients using combined drospirenone + resveratrol therapy compared with the endometrium of patients using oral contraceptives alone. CONCLUSION: These results suggest that resveratrol potentiates the effect of oral contraceptives in the management of endometriosis-associated dysmenorrhea by further decreasing aromatase and cyclo-oxygenase-2 expression in the endometrium.

Role of inflammation and aromatase expression in the eutopic endometrium and its relationship with the development of endometriosis.

Epigenetic changes favoring the transcription of the aromatase gene in the endometrium allow endometrial cells to survive in ectopic locations by producing estrogens that spare them from destruction through activated macrophages. Local estrogen production hastens prostaglandin synthesis by stimulating COX-2 activity, thus creating a self-perpetuating sequence of augmented estrogen formation and enhanced inflammation. Repetitive retrograde menstruation reintroduces aromatase-positive endometrial cells endowed with the capacity to implant and invade the peritoneum. In order to control endometriosis, an effective medication must inhibit aromatase, block COX-2, decrease fibrosis and induce amenorrhea. Within this framework, progestins, either alone or in the form of oral contraceptives, appear as first-line treatment for endometriosis owing to their capacity to block enzymes such as aromatase and COX-2.