Hypersensitivity reaction to Abiraterone, successful desensitization protocol in prostate cancer patient.

INTRODUCTION: In prostate cancer, androgens are key in the growth of both normal prostate and cancer cells. Abiraterone acetate inhibits CYP17, an important target in prostate cancer given its central role in the production of adrenal and tumor-derived androgens. Although abiraterone is generally well tolerated, common adverse effects such as hypertension, hypokalemia, and hepatotoxicity have been reported. CLINICAL CASE: We present the case of an 83-year-old Mexican man with high-volume EC IV prostate cancer resistant to castration, orchiectomy, and bone, liver, and lung metastases. First-line treatment with the CHAARTED scheme was indicated, by patient decision refuse chemotherapy treatment. On the fourth day of starting treatment, he developed pruritic erythematous macular skin lesions and urticaria on the posterior chest that resolved spontaneously. A generalized erythematous and pruritic maculopapular rash appeared 12 days after starting abiraterone, for which she was referred to allergies. MANAGEMENT AND RESULTS: An oral provocation test was performed for two days, presenting localized macular lesions eight hours after the administration of abiraterone. An oral desensitization protocol was carried out for ten days in which no hypersensitivity reactions were observed, thus achieving the successful administration of abiraterone.

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives / Alterações na densidade mineral óssea e nos marcadores de formação óssea em adolescentes usuárias ou não de contraceptivos hormonais orais combinados por período de um ano

Abstract Objective: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. Methods: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n = 42) (20 µg EE/150 µg desogestrel), oral contraceptives 2 (n = 66) (30 µg EE/3 mg drospirenone), and a control group (n = 70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. Results: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. Conclusion: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Resumo: Objetivo: O objetivo deste estudo foi avaliar os efeitos de dois contraceptivos orais combinados de baixa dosagem por um ano sobre o metabolismo ósseo em adolescentes. Métodos: Este foi um estudo quase experimental. As adolescentes foram divididas em três grupos: contraceptivos orais 1 (n = 42) (20 µg de EE/150 µg de desogestrel), contraceptivos orais 2 (n = 66) (30 µg EE/3 mg de drospirenona) e grupo controle (n = 70). As adolescentes foram submetidas à avaliação antropométrica e densitometria (raio-X de dupla energia). Foram avaliados a idade óssea e os marcadores de formação óssea (osteocalcina e fosfatase alcalina óssea). As usuárias de contraceptivos orais foram novamente avaliadas após 12 meses. A análise de regressão linear foi utilizada para estudar, indiretamente, o efeito de cada ano adicional da idade cronológica sobre as variáveis antropométricas e densitométricas e sobre os marcadores ósseos no grupo de controle. Resultados: No início do estudo, não foram observadas diferenças significativas nas variáveis analisadas entre as usuárias de contraceptivos orais 1, contraceptivos orais 2 e o grupo controle. A análise de regressão linear mostrou um aumento na densidade mineral óssea e no conteúdo mineral ósseo para cada ano adicional. Houve uma redução significativa nos níveis de fosfatase alcalina óssea e não foi observada diferença significativa para osteocalcina nos indivíduos controles. A comparação das variáveis do raio-X de dupla energia no início e após um ano não mostrou diferença significativa no grupo de contraceptivos orais 1 ou contraceptivos orais 2. Foi observada uma redução significativa nos níveis de fosfatase alcalina óssea e osteocalcina nos dois grupos contraceptivos orais 1 e contraceptivos orais 2. Conclusão: As adolescentes atingiram o pico de massa óssea durante essa fase da vida. Duas formulações de contraceptivos hormonais orais de baixa dosagem, após um ano de uso, se associaram a menor incremento na densidade mineral óssea e menor concentração de marcadores de formação óssea quando confrontados com resultados de adolescentes não usuárias de contraceptivos.

Autoimmune Progesterone Dermatitis: A Case Report.

INTRODUCTION: Autoimmune progesterone dermatitis (APD) is a rare autoimmune dermatosis characterized by recurrent cutaneous and mucosal lesions during the luteal phase of the menstrual cycle that disappear some days after the menses. CASE REPORT: A 34-year-old primipara woman with no significant past medical history and no prior exogenous hormone use, who presented with cyclic skin eruptions starting 1 year after the delivery. The lesions occurred ∼ 6 days before the menses and disappeared in between 1 and 2 days after the menstruation ceased. The patient was diagnosed after a positive response to an intradermal test with progesterone and was successfully treated with combined oral contraceptives. The skin eruptions have not returned since the initiation of this therapy. CONCLUSION: Dermatologists, gynecologists, and obstetricians should be aware of this rare entity. Furthermore, if this condition is suspected, a thorough history taking on the menstrual cycle and results of the intradermal progesterone test are mandatory.

Autoimmune progesterone dermatitis: A case report

Abstract Introduction Autoimmune progesterone dermatitis (APD) is a rare autoimmune dermatosis characterized by recurrent cutaneous and mucosal lesions during the luteal phase of the menstrual cycle that disappear some days after the menses. Case Report A 34-year-old primipara woman with no significant past medical history and no prior exogenous hormone use, who presented with cyclic skin eruptions starting 1 year after the delivery. The lesions occurred 6 days before the menses and disappeared in between 1 and 2 days after the menstruation ceased. The patient was diagnosed after a positive response to an intradermal test with progesterone and was successfully treated with combined oral contraceptives. The skin eruptions have not returned since the initiation of this therapy. Conclusion Dermatologists, gynecologists, and obstetricians should be aware of this rare entity. Furthermore, if this condition is suspected, a thorough history taking on the menstrual cycle and results of the intradermal progesterone test are mandatory.

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives.

OBJECTIVE: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. METHODS: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n=42) (20µg EE/150µg desogestrel), oral contraceptives 2 (n=66) (30µg EE/3mg drospirenone), and a control group (n=70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. RESULTS: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. CONCLUSION: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies.

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation antiandrogen therapies with either enzalutamide or abiraterone. MATERIALS/METHODS: In a retrospective study, we analyzed patients who received Radium-223 as part of an early-access trial, and following FDA approval in May 2013, patients receiving Radium-223 as part of standard care. Radium-223 was given at standard dosing of 50 kBq/kg each month for 6 total cycles. Complete blood counts were performed before treatment monthly and following each injection. Blood counts from patients receiving Radium alone and concurrently with next-generation antiandrogens were compared. To date, 25 total patients were analyzed, with a median of 5 monthly doses received per patient. Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide (n=8) or abiraterone (n=6). RESULTS: Six patients expired due to disease progression. Two patients discontinued treatment due to grade 3 myelosuppression. For patients receiving either Radium alone and with concurrent next-generation antiandrogen therapy, there did not appear to be any statistically significant differences between initial and nadir blood counts. Mean change from initial neutrophil count to nadir was 1.9×10/L in patients receiving Radium alone, versus 2.3×10/L in patients receiving concurrent therapy (P=0.77). Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone, versus 1.8 g/L in patients receiving concurrent therapy (P=0.31). Mean change from initial platelet count to nadir was 52.3×10 cells/L in patients receiving Radium alone versus 70.6×10 cells/L in patients receiving concurrent therapy (P=0.39). Individual blood counts for each measured laboratory are included in the supplemental data. PSA was stable or decreased in 22% of patients receiving Radium alone versus 35% of patients receiving combination treatment (P=0.24). CONCLUSIONS: Concurrent administration of Radium-223 and next-generation antiandrogen therapies appears to be well tolerated with similar toxicities to standard administration of Radium-223 alone. This particular cohort of patients represents a high-risk, heavily pretreated group of patients with advanced metastatic disease and significant marrow burden. Despite these risk factors, hematologic toxicity was modest and was in the range expected for this risk group based on previous trials. To date, this is the first study investigating the toxicity of combination treatment. Further studies investigating the safety and efficacy of combination treatments are warranted.

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.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats.

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Effects of two contraceptives containing drospirenone on blood pressure in normotensive women: a randomized-controlled trial.

OBJECTIVE: Drospirenone (DRSP) is a progestogen derived from spironolactone with antimineralocorticoid action that seems to exert a favorable effect on blood pressure (BP); however, when associated with ethinylestradiol (EE), this effect does not seem to occur. This study aimed to assess possible differences in BP associated with the use of combined oral contraceptives containing DRSP with different doses of EE. MATERIALS AND METHODS: This open-label parallel-group randomized clinical trial involved women randomized to use either 30 mcg of EE+DRSP (n=22) or 20 mcg of EE+DRSP (n=22). Daytime, nighttime, and 24-h BP were evaluated by ambulatory blood pressure monitoring at the beginning of the trial and 6 months after drug therapy. RESULTS: The groups were similar in terms of demographic characteristics. The mean 24-h systolic blood pressure and diastolic blood pressure (DBP) were similar between the groups before and after treatment (P>0.05). With respect to day and nighttime systolic blood pressure and DBP, no statistically significant difference was observed in BP values between the two groups either before or after treatment, except for the daytime DBP in the 30EE+DRSP group. In this group, a decrease of 2 mmHg (3%) in daytime DBP was observed after 6 months of drug therapy (P=0.04). CONCLUSION: There was no difference in BP associated with the use of combined oral contraceptives containing DRSP irrespective of the EE dose used.

Low-dose oral or non-oral hormone therapy: effects on C-reactive protein and atrial natriuretic peptide in menopause.

OBJECTIVE: To assess the effects of oral low-dose and non-oral hormone therapy (HT) on ultra-sensitive C-reactive protein (CRP), atrial natriuretic peptide (ANP), and cardiovascular risk factors in postmenopause. METHODS: In this randomized, cross-over study, 44 recently postmenopausal women, with no clinical evidence of cardiovascular disease, received oral low-dose HT (estradiol 1 mg + drospirenone 2 mg/day) for 3 months. Forty-two patients received non-oral, conventional HT (1.5 mg/day percutaneous 17ß-estradiol gel or equivalent for nasal route) for 3 months followed by 200 mg/day micronized progesterone by the vaginal route (14 days during each menstrual period). After 3 months, patients were crossed over without washout. Post-HT vs. pre-HT measures were determined: lipids, glucose, body mass index, waist circumference, fibrinogen, CRP-stratified levels, and ANP levels. The study was registered at clinical trials.gov (NCT01432028). RESULTS: The mean age was 51 ± 3 years and the mean time since the menopause was 22 ± 10 months. CRP-stratified high levels decreased in a higher number of non-oral HT patients, who moved to intermediate and low levels (p = 0.02). No effect of HT was observed on ANP levels (baseline 67.4 (18.4-104.5), low-dose oral 43.5 (14.4-95.9), non-oral 39.8 (15.5-67.5) pg/ml). Markers of endothelial function did not worsen with either low-dose oral or non-oral HT: von Willebrand factor (baseline 118 ± 37%, low-dose oral 119 ± 38%, non-oral 108 ± 3%, p < 0.01), fibrinogen (baseline 356 ± 58 mg/dl; low-dose oral 343 ± 77 mg/dl; non-oral 326 ± 71 mg/dl, p < 0.01). CONCLUSIONS: Low-dose oral and non-oral HT for 6 months had neutral or beneficial effects in recently postmenopausal women with no clinical evidence of cardiovascular disease.

Different Pearl Indices in studies of hormonal contraceptives in the United States: impact of study population.

OBJECTIVE: To examine the impact of subject characteristics on efficacy as measured by the Pearl Index (PI) in clinical trials and to make study populations similar by matching. METHODS: Our analysis used US data from four large Phase III studies. We compared results from one fertility control patch study with pooled data from three studies with virtually identical design on oral hormonal contraceptives. First, we identified three characteristics that had the most impact on the PI. Second, we used these three variables and matched subjects from the patch study with those from the oral contraceptive (OC) studies. Finally, we calculated the PIs for matched and unmatched subjects from both the patch study and the OC studies. RESULTS: A total of 3706 subjects were included in our analysis. The variables 'Hispanic ethnicity', 'previous pregnancy' and 'previous use of hormonal contraceptives' had the most impact on the PI. The PIs for the matched patch cohort and the matched OC cohort were 2.97 and 2.48, respectively. Those for the unmatched patch cohort and the unmatched OC cohort were 10.17 and 0.90, respectively. CONCLUSION: Subject characteristics strongly influence the PI in clinical studies of hormonal contraceptives. In particular, Hispanic ethnicity, previous pregnancies and no previous use of hormonal contraceptives result in a higher PI. IMPLICATIONS: PIs from different clinical trials cannot be meaningfully compared unless subject characteristics that have most impact on the PI are similar or are made to be similar statistically as we did here by matching.

Fat mass and obesity-associated gene polymorphisms do not affect metabolic response to hormone therapy in healthy postmenopausal women.

OBJECTIVE: To determine whether fat mass and obesity-associated gene polymorphisms rs9939609 T>A and rs8050136 A>C or their haplotypes influence anthropometric and metabolic variables in recently postmenopausal women receiving hormone therapy. STUDY DESIGN: In this randomized crossover study carried out in a university clinic, 86 postmenopausal women consulting for symptoms of estrogen deficiency were genotyped by real-time polymerase chain reaction for single nucleotide polymorphisms rs9939609 T>A and rs8050136 A>C of the fat mass and obesity-associated gene. Haplotypes were constructed from the combination of polymorphisms rs9939609 and rs8050136, and their frequencies were inferred using the PHASE 2.1.1 program. Participants were clinically evaluated before and after 6 months of hormone therapy to determine body mass index (current kg/m(2)) and waist circumference, blood pressure, lipid profile (total cholesterol, HDL cholesterol and triglycerides) plasma glucose (oral glucose tolerance test), and insulin. Blood samples were also drawn for ultra sensitive C reactive protein. The lipid accumulation product index was calculated as (waist [cm] - 58) × triglyceride concentration (mmol/L). Non-normally distributed parameters were log10 transformed before statistical analysis. Measurements at baseline and at follow-up were compared with ANOVA for repeated measures. Data were considered significant at P<0.05. RESULTS: In women with the homozygous polymorphic AA genotype of the single nucleotide polymorphisms rs9939609 and the wild AA genotype of the single nucleotide polymorphisms rs8050136, lipid accumulation product index and ultra sensitive C reactive protein were higher before hormone therapy in comparison with women with other genotypes from the same single nucleotide polymorphisms group. There was no worsening of any of the anthropometric or metabolic variables, and lipid accumulation product index improved slightly after hormone therapy in SNP rs9939609 (P=0.03) and haplotype AAAA. No changes were observed after hormone therapy in SNP rs8050136. CONCLUSIONS: The presence of fat mass and obesity-associated gene risk variants in healthy early postmenopausal women does not adversely affect their response to hormone therapy.

Drospirenone and levonorgestrel in combination with either 30 or 20 mcg ethinylestradiol reduce soluble adhesion molecules in Brazilian women; cross-sectional study.

BACKGROUND: The objective of this study was to evaluate the effect of three contraceptive pills containing ethinylestradiol (EE) (20 or 30 mcg) in combination with drospirenone (DRSP) and levonorgestrel (LNG) on plasma concentration of adhesion molecules vascular cell adhesion molecule -1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. STUDY DESIGN: A cross-sectional study was conducted with 72 participants (18-30 years old) distributed into three groups that used oral contraceptives containing EE 20 or 30 mcg combined with DRSP 3 mg or EE 30 mcg/LNG 150 mcg for at least 6 months. The control group was comprised of nonusers of contraceptives. Soluble VCAM-1, soluble ICAM-1 and soluble E-selectin were evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared to the control group, a significant decrease was found in VCAM-1 and ICAM-1 concentrations with use of DRSP/20 EE and LNG/30 EE. CONCLUSIONS: DRSP/20 EE and LNG/30 EE induce favorable changes in endothelial function.

Cellular and humoral immune responses after short-term oral hormone therapy in postmenopausal women.

OBJECTIVE: To evaluate the cellular and humoral immune responses after oral hormone therapy in postmenopausal women. Study design This was a prospective cohort study, with intervention. The main outcome measures were delayed-type IV cell-mediated hypersensitivity, leukocytes, immunoglobulins, interleukin-6 (IL-6) and interleukin-10 (IL-10). METHODS: The delayed-type cell-mediated hypersensitivity was measured by using five common allergens before and after 3 months of hormone therapy. Each type of leukocyte cell was counted before and after hormone therapy. Different subtypes of lymphocytes were determined by flow cytometry. Immunoglobulins G, A and M were measured by nephelometry; immunoglobulin E was measured by electrochemiluminescence. IL-6 and IL-10 concentrations were determined by chemiluminescence. RESULTS: Hormone therapy increased the response to tuberculin antigen without changing the total number of leukocytes, eosinophils, neutrophils, lymphocytes, and CD4 +, CD8 + B cells. Both monocyte number and CD4 + /CD8 + ratio suffered a slight modification (p = 0.057). Immunoglobulins A, M and E remained unchanged and immunoglobulin G decreased (p = 0.029). IL-6 levels remained stable but IL-10 concentrations increased significantly after hormone therapy. CONCLUSION: Short-term oral hormone treatment has no impact on the cellular immune response but, concerning the humoral immune response, immunoglobulin G decreased and the levels of IL-10 were significantly higher.

Effects of drospirenone/estradiol on steroid receptors and Bcl-2 in the postmenopausal endometrium.

OBJECTIVE: To evaluate the effect of drospirenone with 17ß-estradiol on the histology and expression of estrogen and progesterone receptors and of Bcl-2 protein, in endometrium of postmenopausal women. METHOD: Forty postmenopausal women, including controls, participated in this study evaluating oral hormone replacement treatment combining 2 mg/day of drospirenone with 1 mg/day of 17ß-estradiol administered for a 24-week period. The effect on the endometrium was assessed by histology and the apoptosis marker Bcl-2. The immunoexpression of estrogen (ER) and progesterone (PR) receptors in the endometrium was also measured. RESULTS: No increase in endometrial thickness was evident after either treatment, although endometrial histology was atrophic in most biopsies. The drospirenone/estradiol group showed higher expression of ER and PR in glandular epithelium compared to stroma, but the Bcl-2 protein was more immunoreactive in stroma than in glandular epithelium. Compared to controls, drospirenone/estradiol users showed higher immunoexpression of ER, PR and Bcl-2 in both glandular epithelium and endometrial stroma. CONCLUSION: A 24-week course of drospirenone with 17ß-estradiol resulted in low proliferation and was shown to lead to atrophic endometrium. The novel progestogen drospirenone seems to have favorable effects on the endometrium of postmenopausal women due to its pro-apoptotic action in glandular epithelium.

Experiencia piloto con el uso extendido de un anticonceptivo oral combinado de baja dosis de estrógeno / Extended use of an oral combined contraceptive pill with low estrogen dose: pilot experience

Objetivo: Evaluar en una experiencia piloto la aceptabilidad y bienestar de la usuaria, después de un periodo de 12 meses de un anticonceptivo hormonal combinado oral de baja dosis estrogénica, con modalidad de uso extendido de 84 píldoras activas consecutivas, seguidas de 7 días de placebo. Método: Se incorporan 25 mujeres voluntarias que usan una combinación de 20 ug de etinilestradiol + 3 mg de drospirenona, con un tiempo de uso de 12 meses. En calendario de registro diario se consignan los días de sangrado o goteo genital así como todo tipo de fármaco ingerido. Al término de los 12 meses se efectúa una encuesta respecto al grado de satisfacción con la posología recibida. Resultados: 13 usuarias (52 por ciento) cumplen los 12 meses de uso. Todas ellas manifiestan un alto grado de conformidad, destacando las ventajas de presentar periodos menstruales ocasionales, mejoría marcada en la sintomatología compatible con el síndrome de tensión premenstrual con el consiguiente incremento del bienestar general. Siete usuarias (28 por ciento) no terminan el estudio por razones médicas, siendo 6 de estas por alteraciones de los flujos rojos y en 5 casos (20 por ciento) se producen retiros no médicos. Conclusión: Esta experiencia, que es la primera con la formulación descrita, confirma en un porcentaje de usuarias las bondades adicionales reportadas en las experiencias previas con otros productos similares, respecto al uso extendido de anticoncepción hormonal oral en un grupo de mujeres que deseaban espaciar sus periodos menstruales.

Objetives: A pilot study designed in order to know about the acceptability of an oral combined contraceptive pill, with low estrogen dose used in an extended way of 84 consecutive days, followed by 7 days of no pills ingestion during a scheduled follow up of 1 year. Methods: 25 volunteers women were recruited among those which wants to use oral combined contraceptive pills and who accepted this extended way of use. Combined contraceptive pills contains each 20 ug of ethinylestradiol plus 3 mg of drosperinone. At admission women were provided with menstrual diary cards in order to check all bleeding days plus any extra pharmaceutical compound received. At the end of the 12 months follow up an interview was done in order to know women experiences and acceptability of this extended way of use. Results: 52 percent of women end the study at the scheduled 12 months use. All of them feel that the main advantages of these extended way of use were to have few menstrual periods and improving premenstrual symtomatology with better quality of life. 7 women (28 percent) did not finish the study because of medical reasons being due in 6 of these for bleeding disturbances. Conclusions: This report is pioneer with the use this hormone combination in this extended type way of use. Results confirm previous positive reports experiences using another similar hormonal compounds with this extended way of use in women who want to reduce the interval of their menstrual periods.

[Combined hormonal contraception in cycles artificially extended]. / Anticoncepción con hormonales combinados en ciclos extendidos artificialmente.

OBJECTIVE: To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. MATERIAL AND METHODS: Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. CONCLUSION: Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.