Geraldez Tomaz

A randomized,open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability

Objective: To compare the effects of continuous combined conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA) with those of tibolone on symptom control, bleeding pattern, lipid profile and tolerability in postmenopausal women. Methods: This was a randomized, open-label, parallel-group, multicenter study. Generally healthy postmenopausal women with an intact uterus and no contraindications to hormone replacement therapy (HRT) or tibolone were enrolled. Each subject was randomly assigned to receive CEE/MPA 0.625 mg-5.0 mg or tibolone 2.5 mg daily for 13 treatment cycles, each of 28 days. Results: A total of 85 subjects were enrolled and received at least one dose of study medication, of which 76 (89.4%) subjects completed the study (n = 40, CEE/MPA; n = 36, tibolone). The incidence of postmenopausal symptoms decreased significantly over time in both treatment groups, compared with baseline, including significant decreases in the incidence of urogenital and sexual health symptoms. Significant differences in symptom control (other than hot flushes) were observed between treatment groups in a few different cycles for different symptoms, but no consistent or clinically significant trends were observed. No statistically significant differences in the incidence of bleeding were observed between treatment groups after cycle 4. Significant decreases in total cholesterol (5.6%) and low-density lipoprotein (LDL) cholesterol (7.5%) were observed at cycle 13, compared with baseline, in the CEE/MPA group, and significant decreases in high-density lipoprotein (HDL) cholesterol (8.5%) and triglycerides (13.7%) were observed at cycle 13, compared with baseline, in the tibolone group. Significant weight gain was observed at cycle 13 in the tibolone group (3.05 kg), compared with the CEE/MPA group (0.96 kg). The incidences of adverse events were similar in both treatment groups. Conclusions: Women treated with CEE/MPA or tibolone showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms, and had similar bleeding patterns after four cycles of therapy. CEE/MPA and tibolone each induced a different mix of changes in the lipid profile.

Estresse e ansiedade em mulheres inférteis

OBJETIVO: avaliar a frequencia de estresse e niveis de ansiedade em mulheres inferteis, de forma a obter subsidios para uma orientacao psicologica especifica. METODOS: estudo transversal envolvendo 152 mulheres inferteis (media de idade 30,3±5,4anos), e 150 controles saudaveis (25,7±7,9 anos). Todas as voluntarias foram avaliadas com a aplicacao do Inventario de Sintomas de Estresse de Lipp e Inventario de Ansiedade Traco-Estado. As variaveis dependentes foram: frequencia de estresse e escores de ansiedade (estado e traco). A analise estatistica compreendeu a utilizacao dos testes c2 e Mann-Whitney, alem de regressao logistica para testar associacoes entre as variaveis dependentes e fatores de risco considerados. O nivel de significância adotado foi de 5%. RESULTADOS: a frequencia de estresse foi maior no grupo infertilidade em relacao ao grupo controle (61,8 e 36,0%, respectivamente), no entanto, nao foram observadas diferencas significativas entre os grupos com relacao as fases do estresse e tipo de sintomatologia predominante. Em relacao a ansiedade, nao houve diferencas significativas entre os grupos infertilidade e controle quanto as medianas dos escores de estado (39,5 e 41,0, respectivamente) e traco (44,0 e 42,0, respectivamente) de ansiedade. No grupo infertilidade, os fatores de risco associados significativamente com estresse ou ansiedade foram: desconhecimento do fator causal, fase de investigacao diagnostica e ausencia de filhos advindos de outros casamentos. CONCLUSOES: as mulheres inferteis estao mais vulneraveis ao estresse, no entanto, sao capazes de responder aos eventos estressores de forma adaptativa, sem comprometimentos mais serios nas areas fisica e psicologica.

Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate

Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.

Assessing the benefits of rosiglitazone in women with polycystic ovary syndrome through its effects on insulin-like growth factor 1, insulin-like growth factor-binding protein-3 and insulin resistance: a pilot study

The physiopathology of insulin resistance in women with polycystic ovary syndrome (PCOS) is related to a disturbance in the function of the insulin receptor. In fact, the post-receptor defect associated with PCOS may be a critical factor that interferes with the recruitment of proteins for intracellular glucose transport. The conceivable end result is a compensatory increase in insulin (1). One possible option for correcting this insulin resistance is the use of drugs (such as metformin and glitazones) that may increase glucose intake in the tissue (1,2). However, there are studies showing that a few patients interrupted their metformin treatment due to a high incidence of gastrointestinal side effects, such as nausea or vomiting (2). Rosiglitazone binds to the peroxisome proliferator-activated receptor, which regulates the transcription of many genes, including the glucose transporter, and decreases insulin resistance (4); however, this drug may increase the risk of cardiovascular diseases, such as myocardial infarction. These effects are not reported in patients who have insulin resistance without diabetes (5). It is important to emphasize that endothelial damage is more pronounced in diabetic patients than in non-diabetic ones (6). Approximately 1% of IGF-1 circulates freely in the plasma; the remainder is transported by binding proteins. The efficacy of muscle IGF-1 depends on the expression and availability of a family of six types of binding proteins. In humans, the most important of these proteins is IGFBP-3 (>80%), which is responsible for the maintenance of the circulating IGF-1 levels, along with the ALS glycoprotein, which has great affinity for IGF-1 and -2 (7). The increase in insulin may affect IGF-1 actions. In fact, insulin decreases the production of IGFBP-3 in the liver. Therefore, the free levels of IGF-1 are elevated and may affect ovarian function and increase androgen production (8). The aim of this study was to evaluate the actions of rosiglitazone on IGF-1 and IGFBP-3 in women with PCOS.

Efficacy acceptability and clinical effects of a low-dose injectable contraceptive combination of dihydroxyprogesterone acetophenide and estradiol enanthate.

A total of 1,904 women, aged 15-38, used an injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate, given once during each menstrual cycle between the 7th and 10th day, and preferably on the 8th day of the cycle, for a total of 17,576 cycles. Of these 1,904 women, 1,197 completed 12 cycles of use of the injectable combination. One subject became pregnant during the trial, resulting in a cumulative pregnancy rate of 0.07%. Principal reasons for discontinuation were personal, non-medical reasons, such as lost to follow-up, no longer wished to continue, protocol violation, desire to change to another contraceptive method, moved away, or other personal reasons. Mean weight of 1,901 subjects at admission to the trial was 53.5 +/- 0.2 kg and this increased to 54.3 +/- 0.3 kg after 12 cycles of use. Approximately 50% of subjects experienced menstrual bleeding similar to normal throughout the study period. The most frequent menstrual abnormality was irregular bleeding, experienced by approximately one-third of subjects.

Avaliação da tolerabilidade e do controle de ciclo de dois contraceptivos orais de baixa dose: estudo comparativo aberto

Realizou-se um estudo aberto comparativo em nove centros brasileiros para avaliar a tolerabilidade e o controle de ciclo obtido com o uso de dois contraceptivos orais de baixa dose contendo 20 mg etinilestradiol/75 mg gestodeno e 20 mg etinilestradiol/150 mg desogestrel, durante seis ciclos de tratamento. Foram selecionadas 167 mulheres saudaveis com vida sexual ativa (77 no grupo do gestodeno e 90 no grupo do desogestrel), das quais 138 completaram os seis ciclos de tratamento. Em um subgrupo de novas usuarias realizou-se tambem perfil lipidico e hemostatico. Foram avaliados 867 ciclos no total. Ocorreu sangramento irregular em 4,6% dos ciclos com gestodeno e em 8,1% com desogestrel. A tolerabilidade a ambas preparacoes foi boa, mas houve significativamente mais nausea no grupo do desogestrel. O controle de ciclo foi bom com os dois contraceptivos, sendo que houve frequencia significativamente menor de sangramento irregular no grupo do gestodeno quando se leva em conta que todos os ciclos foram considerados. Nao houve alteracoes clinicamente significativas no perfil hemostatico. O perfil lipidico mostrou tendencia a tornar-se mais favoravel apos seis ciclos de tratamento com as duas preparacoes. Nao ocorreu alteracao no peso medio das mulheres no grupo do gestodeno; no grupo do desogestrel houve aumento significativo no peso medio de aproximadamente 1 kg apos seis meses de tratamento. A adesao ao tratamento foi boa com as duas preparacoes. Os resultados deste estudo mostram que preparacoes contendo baixa dose de gestodeno ou desogestrel associados a 20 mg de etinilestradiol sao contraceptivos bem tolerados que permitem bom controle de ciclo, sem efeitos colaterais significantes.