Luciano de Melo Pompei

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.

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.

Tibolone reduces osteoporotic fracture risk and breast cancer risk, but increases the risk of stroke

Tibolone is a synthetic steroid available for prescription in the last two decades in the Europe and other countries, such as Brazil. It has been used for postmenopausal osteoporosis prevention and for treatment of menopausal symptoms. Tibolone is a progestin that is metabolised in several tissues, forming the metabolites 3a-hydroxytibolone (3a-OH-tibolone) and 3b-hydroxytibolone (3b-OH-tibolone), which bind to the estrogen receptors. These two substances may be sulfated, which inactivates them. The metabolite 3b-OHtibolone, by its turn, may be transformed into D4isomer, which may be also formed directly from tibolone. The D4-isomer presents affinity for progesterone and androgens receptors [1]. This complicated net of esteroidal metabolisation is variable, in accordance with the tissue, depending on the relative concentrations of the enzymes that make such conversions. Thus, for example, in the endometrium, there is predominance of the conversion to D4-isomer and, therefore, the progestational action predominates [2]. The beneficial effect of tibolone in the control of the climacteric symptoms had already been demonstrated by some studies, disclosing reduction of the hot flushes, fatigue, insomnia, headache, among others [1]. On the other hand, and in contrast to that observed with the estroprogestative therapy, there are evidences that tibolone would not stimulate the proliferation of the mammary cells [2,3]. Part of this opinion is due to mammographic density studies, which demonstrated that this steroid did not increase the mammary density, in opposition to estrogen and estroprogestative therapies [4–6]. Even with long-term use of tibolone, as much as 10 years, no increase of mammary density has been shown [7]. With regard to bone metabolism, there are demonstrations of bone mineral density increase, reduction of bone turnover with reduction of the bone loss [8–12]. However, the majority of these studies evaluated relatively small populations and demonstration of reduction of fracture risk lacked, which made the substance has indication for prevention of bone loss and not for postmenopausal osteoporosis treatment [1]. This concept changed in August 2008 with the publication of the paper LIFT (Long-term intervention on fractures with tibolone) in the New England Journal of Medicine. It was a multicentric, multinational, randomised, placebo-controlled study which primarily evaluated the effect of tibolone 1.25 mg/day on the risk of vertebral fracture, and had, as secondary objectives, the evaluation of risks of non-vertebral fracture risk breakings, breast cancer, venous thromboembolism and cardiovascular disease [13]. The LIFT study included 4532 postmenopausal women, aging between 60 and 85 years old (average of 68.3 years) with densitometric osteoporosis according to the World Health Organization (t-score 72.5) or with t-score 72.0 plus radiological vertebral fracture. The inclusion of patients was between June 2001 and July 2003, and in October 2005, the data and safety monitoring board of the study communicated a potential increase of risk of stroke. After this information, 496 patients discontinued study treatment. In February 2006, the data and safety monitoring board recommended the interruption of the study because of an increased risk of stroke and because the effect of treatment on vertebral fracture risk had already met the criteria for stopping the trial for efficacy. According to the published article, the median time of treatment was 34 months, and 91% of the

Brazilian guidelines for the diagnosis and treatment of postmenopausal osteoporosis

Osteoporosis is the leading cause of fractures in the population older than 50 years. This silent disease affects primarily postmenopausal women and the elderly, and the morbidity and mortality rates are high. The main goal of treating osteoporosis is the prevention of fractures. The identification of populations at risk through early diagnosis and treatment is essential. The last Brazilian guideline for the treatment of postmenopausal osteoporosis was elaborated in 2002. Since then, new strategies for diagnosis and risk stratification have been developed, and drugs with novel action mechanisms have been added to the therapeutic arsenal. The Osteoporosis and Osteometabolic Diseases Committee of the Brazilian Society of Rheumatology, in conjunction with the Brazilian Medical Association and other Societies, has developed this update of the guidelines for the treatment of postmenopausal osteoporosis according to the best scientific evidence available. This update is intended for professionals in many medical and health specialties involved in the treatment of osteoporosis, for physicians in general and for health-related organizations.

Attitudes, knowledge and prescribing habits of Brazilian gynecologists regarding extended-cycle oral contraceptives.

Abstract Extended-cycle and continuous use combined oral contraceptives (COC) have been widely investigated; however, gynecologists’ prescribing habits are largely unknown. This study evaluated the opinions and prescribing habits of Brazilian gynecologists regarding extended/continuous COC. Gynecologists caring for reproductive-age women and used to prescribing COC were recruited to an online survey. Overall, 1097 physicians were included. Of these, 93.0% stated that patients requested extended/continuous COC, with 93.9% of the physicians having already prescribed these regimens at least once. Only 67 physicians reported never having prescribed extended/continuous COC. The most common reasons for prescribing extended/continuous COC were “dysmenorrhea”, “endometriosis” and “convenience of menstrual suppression”. Physicians reported prescribing extended/continuous regimens for 20.7 ± 17.2% of their patients with an indication for COC, postgraduate degree holders being more likely to prescribe extended/continuous regimens than physicians without postgraduate degree (23.6 ± 19.1% versus 20.0 ± 16.7%; p = 0.014). In conclusion, the vast majority of gynecologists prescribe extended/continuous COC. Women often request information from their doctors on the subject. “Convenience of menstrual suppression” is a common reason given for prescribing extended/continuous COC. According to the physicians, the great majority of extended/continuous COC users are satisfied or very satisfied with the regimen prescribed.

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-score<or=-2.5 or radiographic fragility fracture within the last year and no treatment with osteoporosis medication in the preceding 3 mo. Patients were treated with once weekly risedronate of 35 mg for 12 wk. Patients also received 1000 mg calcium carbonate and 400 IU vitamin D. The main outcome was the effect on bone resorption, as assessed by the quantification of serum C-telopeptide of type I collagen (CTX). Of the 556 women screened, 480 women received >or=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.

Personality Traits of Postmenopausal Women with Sexual Dysfunction

OBJECTIVE  The aim of the present study is to identify the association between personality traits of postmenopausal women and the occurrence of sexual dysfunction. METHODS  A total of 43 postmenopausal women were evaluated according to their self-perception of the quality of their sexual life. They answered the following questionnaires: Sociodemographic Profile Questionnaire, Female Sexual Function Index (FSFI), Beck Depression Inventory (BDI) and Factorial Personality Inventory (FPI-II). RESULTS  Women with poorer sexual self-perception showed low affective need (p < 0.01) and low need for organization (p < 0.01). Based on the need for control and opposition, there was no difference between the groups. Groups separated by the scores obtained on the FSFI showed no significant differences. CONCLUSION  Postmenopausal women with lower schooling and personality characteristics that demonstrate low affective and organizational needs are more likely to present sexual dysfunction.

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

Abstract 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.

Influence of Dyslipidemia on the Quality of Sexual Life in Women in the Menacme using a Combined Oral Contraceptive.

Purpose Female sexual dysfunction is a complex and common condition that affects women, and the relationship between sexual function and dyslipidemia is poorly studied. This study aims to assess this relationship in the reproductive life women in the menacme who use combined oral contraceptives (COCs). Methods A total of 49 healthy women who were sexually active received COC pills that contained ethinylestradiol 30 mcg (EE30) plus levonorgestrel 150 mcg (LNG150). The women were divided into two groups according to their lipid profiles. Dyslipidemia was defined as a high-density lipoprotein (HDL) level < 50 mg/dL or a low-density lipoprotein (LDL) level > 130 mg/dL. Sexual function was assessed using the Female Sexual Function Index (FSFI) Questionnaire. Lipid and lipoprotein parameters were obtained at baseline and after the sixth cycle. Results After six cycles of the COCs, the total cholesterol and LDL cholesterol levels in the women with a LDL level > 130 mg/dL decreased by 14.7% and 22.1% respectively. In the women with a HDL level < 50 mg/dL at baseline, the HDL level increased by 15.5% at the end of the study. The arousal and orgasm domains and the FSFI total scores significantly increased in women with and without dyslipidemia. The desire and satisfaction domains increased only in the group without dyslipidemia at the end of the treatment period. Conclusions The EE30/LNG150 formulation increased the sexual function and it was only positively correlated with the HDL cholesterol level. These data indicated a low correlation between sexual function and the changes in the lipid and lipoprotein metabolism.

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.