Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial.

OBJECTIVE: Evaluate the effects of ultra-low-dose hormone therapy (Ultra-LD HT) with 17ß-estradiol 0.5 mg and norethisterone acetate 0.1 mg (E2 0.5/NETA 0.1) versus placebo on bone turnover markers (BTM) in postmenopausal women. STUDY DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was performed with 107 participants who received one tablet daily of E2 0.5/NETA 0.1 or placebo for 24-weeks. Bone formation markers-N-terminal propeptide of type I procollagen (PINP) and Bone-specific alkaline phosphatase (BSAP), and bone resorption markers-C-telopeptide of type I collagen (CTX-I) and N-telopeptide crosslinked of type I collagen (NTX) were assessed before and at 12 and 24-weeks of treatment. RESULTS: Women treated with E2 0.5/NETA 0.1 had a significant reduction in the PINP marker from baseline (58.49 ± 21.12 µg/L) to week 12 (48.31 ± 20.99 µg/L) and week 24 (39.16 ± 16.50 µg/L). Placebo group, the PINP marker did not differ significantly. The analysis of the BSAP indicated a significant increase in the placebo group (13.8 ± 5.09 µg/L and 16.29 ± 4.3 µg/L, at baseline and week 24, respectively), whereas in the treatment group the values did not change. The analysis of the NTX marker showed a significant reduction only in the treatment group (43.21 ± 15.26 nM/mM and 33.89 ± 14.9 nM/mM, at baseline and week 24, respectively). CTX-I had a significant decrease in the treatment group from baseline (0.3 ± 0.16 ng/L) to week 12 (0.21 ± 0.14 ng/L) and week 24 (0.21 ± 0.12 ng/L). CONCLUSION: Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, an expected effect during the anti-resorptive therapy, suggesting a protective bone effect with the Ultra-LD HT.

Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women.

OBJECTIVE: The aim of the study was to evaluate efficacy of fractional CO2 vaginal laser treatment (Laser, L) and compare it to local estrogen therapy (Estriol, E) and the combination of both treatments (Laser + Estriol, LE) in the treatment of vulvovaginal atrophy (VVA). METHODS: A total of 45 postmenopausal women meeting inclusion criteria were randomized in L, E, or LE groups. Assessments at baseline, 8 and 20 weeks, were conducted using Vaginal Health Index (VHI), Visual Analog Scale for VVA symptoms (dyspareunia, dryness, and burning), Female Sexual Function Index, and maturation value (MV) of Meisels. RESULTS: Forty-five women were included and 3 women were lost to follow-up. VHI average score was significantly higher at weeks 8 and 20 in all study arms. At week 20, the LE arm also showed incremental improvement of VHI score (P = 0.01). L and LE groups showed a significant improvement of dyspareunia, burning, and dryness, and the E arm only of dryness (P < 0.001). LE group presented significant improvement of total Female Sex Function Index (FSFI) score (P = 0.02) and individual domains of pain, desire, and lubrication. In contrast, the L group showed significant worsening of pain domain in FSFI (P = 0.04), but FSFI total scores were comparable in all treatment arms at week 20. CONCLUSIONS: CO2 vaginal laser alone or in combination with topical estriol is a good treatment option for VVA symptoms. Sexual-related pain with vaginal laser treatment might be of concern.

Evaluation of Quality of life, Physical Activity and Nutritional Profile of Postmenopausal Women with and without Vitamin D Deficiency / Qualidade de vida, atividade física e perfil nutricional de mulheres na pós-menopausa com e sem deficiência de vitamina D

Abstract Introduction Vitamin D deficiency is associated with various diseases. Prevalent in Brazil, it can result from inadequate lifestyle habits. Objective To demonstrate that postmenopausal women with vitamin D deficiency have worse quality of health, expressed as worse quality of life, lower levels of physical activity, and worse nutritional profile. Methods Postmenopausal women answered questionnaires about physical activity and quality of life, provided a 24-hour food record, and had serum vitamin D levels measured. Results Among the more active women, those who perform a daily average of one hour of physical activity had vitamin D levels above 20 ng/mL (76.9%), and those, which expose themselves to sunlight, had vitamin D levels above 30 ng/mL (34.6%). Meanwhile the percentages for the women who are less physically active and less exposed to sunlight were 42.2% and 8.9% respectively. Being more active and more exposed to sunlight resulted in a lower fat percentage. Serum vitamin D levels were not correlated with quality of life. Conclusion Walking and gardening increased serum vitamin D levels and decreased the percentage of body fat. The limitations of the study prevented the impact of 25hidroxyvitamin D on the quality of life and nutritional aspects of the women from being evaluated.

Resumo Introdução A deficiência de vitamina D está associada a diversas doenças. Prevalente no Brasil, pode ser consequência de hábitos de vida inadequados. Objetivo Demonstrar que mulheres na pós-menopausa com hipovitaminose D têm pior qualidade de saúde, expressa por piores qualidade de vida, nível de atividade física e perfil nutricional. Métodos Mulheres na pós-menopausa responderam a questionários sobre atividade física, qualidade de vida, registro alimentar de 24 horas, e tiveram os níveis séricos de vitamina D medidos. Resultados Dentre as mulheres mais ativas, as que praticam em média 1 hora de atividade por dia apresentaram níveis de vitamina D superiores a 20 ng/mL (76,9%), e as que se expõem ao sol apresentaram níveis acima de 30 ng/mL (34,6 %). Já as mulheres menos ativas e menos expostas ao sol apresentaram respectivamente 42,2 % e 8,9%. Ser mais ativa e ter maior exposição solar significou ter menor percentual de gordura. O nível sérico de vitamina D não mostrou relação com a qualidade de vida. Conclusão Caminhada e jardinagem aumentam os níveis séricos de vitamina D e diminuem o percentual de gordura corpórea. As limitações do estudo não permitiram avaliar o impacto da 25-hidróxi-vitamina D na qualidade de vida e nos aspectos nutricionais das mulheres.

Evaluation of Quality of life, Physical Activity and Nutritional Profile of Postmenopausal Women with and without Vitamin D Deficiency.

Introduction Vitamin D deficiency is associated with various diseases. Prevalent in Brazil, it can result from inadequate lifestyle habits. Objective To demonstrate that postmenopausal women with vitamin D deficiency have worse quality of health, expressed as worse quality of life, lower levels of physical activity, and worse nutritional profile. Methods Postmenopausal women answered questionnaires about physical activity and quality of life, provided a 24-hour food record, and had serum vitamin D levels measured. Results Among the more active women, those who perform a daily average of one hour of physical activity had vitamin D levels above 20 ng/mL (76.9%), and those, which expose themselves to sunlight, had vitamin D levels above 30 ng/mL (34.6%). Meanwhile the percentages for the women who are less physically active and less exposed to sunlight were 42.2% and 8.9% respectively. Being more active and more exposed to sunlight resulted in a lower fat percentage. Serum vitamin D levels were not correlated with quality of life. Conclusion Walking and gardening increased serum vitamin D levels and decreased the percentage of body fat. The limitations of the study prevented the impact of 25-hidroxyvitamin D on the quality of life and nutritional aspects of the women from being evaluated.

Introdução A deficiência de vitamina D está associada a diversas doenças. Prevalente no Brasil, pode ser consequência de hábitos de vida inadequados. Objetivo Demonstrar que mulheres na pós-menopausa com hipovitaminose D têm pior qualidade de saúde, expressa por piores qualidade de vida, nível de atividade física e perfil nutricional. Métodos Mulheres na pós-menopausa responderam a questionários sobre atividade física, qualidade de vida, registro alimentar de 24 horas, e tiveram os níveis séricos de vitamina D medidos. Resultados Dentre as mulheres mais ativas, as que praticam em média 1 hora de atividade por dia apresentaram níveis de vitamina D superiores a 20 ng/mL (76,9%), e as que se expõem ao sol apresentaram níveis acima de 30 ng/mL (34,6 %). Já as mulheres menos ativas e menos expostas ao sol apresentaram respectivamente 42,2 % e 8,9%. Ser mais ativa e ter maior exposição solar significou ter menor percentual de gordura. O nível sérico de vitamina D não mostrou relação com a qualidade de vida. Conclusão Caminhada e jardinagem aumentam os níveis séricos de vitamina D e diminuem o percentual de gordura corpórea. As limitações do estudo não permitiram avaliar o impacto da 25-hidróxi-vitamina D na qualidade de vida e nos aspectos nutricionais das mulheres.

Effects of two combined hormonal contraceptives with the same composition and different doses on female sexual function and plasma androgen levels.

BACKGROUND: This study was conducted to compare the effects of two contraceptive pills with different doses of the same components, on plasma androgen levels and female sexual function among women without previous sexual dysfunction. STUDY DESIGN: The participants were randomized into two groups, to receive pills containing ethynylestradiol (EE) 30 mcg and levonorgestrel (LNG) 150 mcg or EE 20 mcg and LNG 100 mcg, for six cycles. Sexual function was assessed using a standardized questionnaire [Female Sexual Function Index (FSFI)]. Hormone assays were performed at baseline and after the sixth cycle. RESULTS: Forty-nine women were included in the EE30/LNG150 group and 48 in the EE20/LNG100 group. EE30/LNG150 group presented 54% and 67% decreases of total testosterone and free androgen index, respectively, with statistical significance. EE20/LNG100 presented reductions of 20% and 42%, respectively, but without statistical significance. Both groups showed improvements in the FSFI "desire" score, but with statistical significance only for EE20/LNG100 group. CONCLUSIONS: EE30/LNG150 decreased plasma androgen levels, but there was no impairment in sexual desire, on the other hand, sexual desire score increased with EE20/LNG100 formulation.

Clinical and morphological factors predictive of occult involvement of the nipple-areola complex in mastectomy specimens.

OBJECTIVE: To evaluate characteristics predictive of nipple-areola complex (NAC) involvement by the breast tumor. STUDY DESIGN: Cases of infiltrative ductal carcinoma (stages I, IIA and IIB) treated by mastectomy in which the distance between the tumor and the NAC was >or=2 cm were included. NAC involvement was evaluated using serial histological sections. The distance between the tumor and the NAC was measured on mammograms. Other parameters taken into consideration were: tumor size, histological and nuclear grades, vascular invasion, and the presence of an in situ component. For comparisons between categorical variables, the chi-square test or Fisher's exact test were used. Student's t-test was used for numerical variables with normal distribution and the Mann-Whitney U-test was applied when distribution was not normal. RESULTS: Fifty patients were included. NAC was affected in 12 and unaffected in 38. There was no statistically significant difference in mean age between the unaffected and affected groups (58.9+/-13.5 years versus 55.8+/-12.5 years, p=0.477); however, 13.2% and 58.3% (p=0.046) in the NAC-unaffected and NAC-affected groups, respectively, were <50 years of age. Distance

Effects of short-term risedronate on bone resorption and patient satisfaction in postmenopausal osteoporosis patients.

This multicenter, open-label study evaluated the effects of short-term risedronate on bone resorption and patient satisfaction in postmenopausal women with osteoporosis in Brazil. Entry requirements included: osteoporosis of the spine/femoral neck diagnosed by a bone mineral density (BMD) T-scoreor=1 dose of study drug (intent-to-treat [ITT] population), and 390 completed treatment (81%). After 12 wk, CTX decreased in 94% of patients (from 0.419+/-0.234 to 0.158+/-0.171 microg/L, p<0.0001). Mean CTX reduction was 60.6%. Patient satisfaction was good/excellent in 91.7% of patients. A total of 156 adverse events (AEs) were reported by 113 (23.5%) patients in the ITT population. Digestive symptoms emerged or worsened in 7.1% and 3.5%, respectively. Five patients (1.0%) experienced serious AEs, not considered to be related to risedronate. In conclusion, risedronate significantly reduced serum CTX after 12-wk treatment. Almost all patients reported good/excellent satisfaction.

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow.

OBJECTIVES: To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy. METHODS: A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2mg oral micronized estradiol (E2) (n=25); (B) 2mg oral E2+1mg oral norethisterone acetate (NETA) (n=28); or C) placebo (n=24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography. RESULTS: Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E2, E2+NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E2, E2+NETA and placebo groups, respectively (p<0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E2 group and increased 12.9% and 16.0% in the E2+NETA group (p<0.05), respectively. Carotid PI following treatment was 1.18+/-0.23, 1.38+/-0.20 and 1.41+/-0.21 for the E2, E2+NETA and placebo groups, respectively (p=0.0006). CONCLUSIONS: Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated.

Morphometric evaluation of effects of two sex steroids on mammary gland of female rats.

OBJECTIVE: The purpose of this study was to evaluate the effects of two sex hormones on normal mammary gland of female rats. METHODS: Forty 250-day-old female rats, 20 of them with offspring and 20 not, were ovariectomized and, divided into 4 subgroups in order to receive one of the following subcutaneous treatment: estradiol benzoate (EB), medroxyprogesterone (MPA), EB+MPA or placebo, for 10 weeks. After treatment, mammary glands were studied with optical microscope. Whole gland, lobule, ductule and lumen compartments were evaluated by morphometric methods. Also a qualitative evaluation were performed seeking for secretion, microcalcification and trophic status. RESULTS: It was found that (a) MPA-only and placebo were similar for all parameters; (b) the same between EB and EB+MPA; (c) EB and EB+MPA increased lobule, ductule and lumen compartments significantly compared to MPA-only or placebo; (d) EB increased epithelium but without significance and EB+MPA increased it significantly compared to placebo or MPA; (e) EB and EB+MPA incremented secretion. CONCLUSIONS: In normal mammary gland of female rats: progestin action depends on estrogen presence. MPA does not revert estrogen-dependent proliferation, but it magnifies estradiol effect. Both EB and EB+MPA stimulate differentiation. Rats without offspring presented a greater epithelial proliferation under treatment with these sex hormones.

Effects in post-menopausal women of transdermal estrogen associated with progestin upon the removal from the plasma of a microemulsion that resembles low-density lipoprotein (LDL).

OBJECTIVE: To evaluate the effects of transdermal estradiol and medroxyprogesterone acetate (MPA) treatment on the removal from the plasma of a cholesterol-rich microemulsion (LDE) that roughly resembles low-density lipoprotein (LDL) structure and that binds to LDL receptors. METHODS: Ten healthy post-menopausal women were studied before and after 3-month treatment with transdermal estradiol in the following dosages administered every 3.5 days: 25, 50, 50, 100, 100, 50, 50 and 25 microg. From the 15th to the 21st day and from the 22nd to the 28th day of estrogen treatment, respectively, 10 and 5 mg q.d. MPA per oral were associated to the transdermal estrogen. The emulsion labeled with 14C-cholesteryl oleate was injected after 12 h fasting and its fractional catabolic rate (FCR) was calculated from the plasma decaying curves of the isotope. RESULTS: Treatment reduced LDL-cholesterol levels by 8% only (149.0 +/- 36.0 mg/dl, 138.0 +/- 27.0 mg/dl; P = 0.046), but the FCR of LDE expressed in medians (25%; 75%) increased from 0.0054 (0.003; 0.052) h(-1) to 0.021 (0.009; 0.10) h(-1), P = 0.002. CONCLUSION: The association used in this study so as to mimic the increasing-decreasing pattern of the hormonal ovarian production reduced modestly LDL-cholesterol levels but pronouncedly increased the lipoprotein removal as tested by LDE FCR.