Postmenopausal androgen-secreting ovarian tumors: challenging differential diagnosis in two cases.

Postmenopausal hyperandrogenism constitutes a very rare condition of tumoral or non-tumoral origin primarily residing either in the ovary or in the adrenal glands. We present herein two cases with this condition; one with abnormal postmenopausal genital bleeding and mild increase in facial hair, and the second with slow-developing hirsutism and virilization. Both cases shared a notorious increase in libido. The laboratory tests showed high levels of testosterone (>100 ng/ml). A normal value of dehydroepiandrosterone sulfate and a normal cortisol level at 9 am after 1 mg of dexamethasone administered at midnight (Nugent test) made an adrenal etiology very unlikely. On the other hand, a high level of inhibine B oriented to an ovarian source. Transvaginal sonography failed to demonstrate an ovarian tumor, but an abdominal and pelvic computed tomography scan or magnetic resonance imaging detected an ovarian tumor and normal adrenal glands. A laparoscopic oophorectomy was performed, and the histological study demonstrated a steroidal cell tumor in the first case and a Leydig cell tumor in the second.

Gynecological-endocrinological aspects in women carriers of BRCA1/2 gene mutations.

Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.

Vaginal Health: Insights, Views & Attitudes (VIVA-LATAM): results from a survey in Latin America.

OBJECTIVE: To investigate awareness in Latin America, knowledge of postmenopausal vaginal atrophy was evaluated in a sample of women from this region. METHODS: A total of 2509 postmenopausal women aged 55-65 years, resident in Argentina, Brazil, Chile, Colombia and Mexico, completed a structured online questionnaire. RESULTS: Over half the surveyed population (57%) reported experiencing symptoms of vaginal atrophy. Only 6% of the overall cohort attributed symptoms of vaginal atrophy directly to the condition, and 71% did not consider the condition to be chronic, resulting in many women not accessing effective therapy. Half the women (49%) affected by vaginal atrophy had used lubricating gels and creams; 36% had used some form of local hormone treatment. To understand symptoms and/or treatment options for vaginal discomfort, the majority of survey participants (92%) were willing to seek advice from health-care professionals; most (61%) felt/would feel comfortable talking to their doctor about this. CONCLUSION: Many women in Latin America lack knowledge of postmenopausal vaginal atrophy, not appreciating the chronic nature of the condition, and may benefit from dialog initiated by health-care professionals to facilitate greater understanding and increased awareness of the availability of effective treatment.

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis.

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed databases for a systematic review of long-duration (at least 6 months), randomized, controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11-0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging.

Oncology in midlife and beyond.

The onset of the menopause is often a time when women's concerns can act as a powerful trigger to encourage healthy modifications in lifestyle which will maintain, or improve, their general health. This document aims to help women to understand their potential risks, to encourage them to find proactive preventive strategies by modifying some of their attitudes, and to use health resources (when available) to be screened. Cancer is an important cause of death but not the primary cause of mortality. Cardio/circulatory diseases represent 35-40% of causes of death in most developed countries and 20-25% of women will die from cancers in Western Europe, Australasia, high-income North America, high-income Asia Pacific, East Asia and Southern Latin America. Breast cancer, lung cancer and colorectal cancer are prevalent in most regions of the world. Cervical cancer remains a hallmark of low access to health care. Preventive strategies (decreasing smoking and alcohol consumption, losing weight, eating a healthy diet and undertaking physical activity) and implementation of screening could help to significantly decrease the incidence of and mortality from cancer. The mortality/incidence ratio is higher in developing countries compared to high-income regions as well as in subgroups of populations in developed countries with lower socioeconomic levels. Implementation of better diagnostic methods and management of cancer according to the local resources will help to decrease the mortality rate in developing countries, and effort has to be made to decrease social inequities and improve access to health care for low-income groups. In conclusion, cancer incidence is increasing as a consequence of longer life expectancy all over the world. National health programs are mandatory to implement screening and to improve individual management. Finally, educating women so that they are aware of ways to improve their general health, to minimize their own risk factors and to identify signs of change in their own health which may be markers of impending cancer will help to reduce the burden of disease and improve the prognosis for tumors detected at an earlier stage.

Understanding weight gain at menopause.

OBJECTIVE: The aim of this review was to summarize the literature regarding the impact of the menopause transition on body weight and body composition. METHODS: We conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2012) for English-language studies that included the following search terms: 'menopause', 'midlife', 'hormone therapy' or 'estrogen' combined with 'obesity', 'body weight' or 'body composition'. RESULTS: Whereas weight gain per se cannot be attributed to the menopause transition, the change in the hormonal milieu at menopause is associated with an increase in total body fat and an increase in abdominal fat. Weight excess at midlife is not only associated with a heightened risk of cardiovascular and metabolic disease, but also impacts adversely on health-related quality of life and sexual function. Animal and human studies indicate that this tendency towards central abdominal fat accumulation is ameliorated by estrogen therapy. Studies mostly indicate a reduction in overall fat mass with estrogen and estrogen-progestin therapy, improved insulin sensitivity and a lower rate of development of type 2 diabetes. CONCLUSION: The hormonal changes across the perimenopause substantially contribute to increased abdominal obesity which leads to additional physical and psychological morbidity. There is strong evidence that estrogen therapy may partly prevent this menopause-related change in body composition and the associated metabolic sequelae. However, further studies are required to identify the women most likely to gain metabolic benefit from menopausal hormone therapy in order to develop evidence-based clinical recommendations.

Non-estrogen conventional and phytochemical treatments for vasomotor symptoms: what needs to be known for practice.

OBJECTIVE: Non-hormonal treatment for menopausal vasomotor symptoms (VMS) is needed in women in whom there are medical or personal concerns on the use of hormone therapy. This paper reviews conventional and phytochemical therapies available for the relief of VMS, on their mechanisms of action, their efficacy and safety concerns. METHODS: Medline was searched through Pubmed on the names of the diverse therapies analyzed, up to June 2011. The Cochrane Controlled Clinical Trials Register Database was searched for relevant trials that provided data on treatment of menopausal hot flushes. RESULTS: All non-estrogen treatments for VMS are less efficacious than estrogen treatment. Randomized trials with neuroendocrine agents show globally modest to moderate reduction of VMS and frequent bothersome adverse events. The variability of effects makes it possible to undergo treatment in search for individual response where estrogen treatment is contraindicated. The antidepressants that interact with cytochrome P450, inhibiting tamoxifen metabolism to endoxifen, interfere with tamoxifen therapy in breast cancer patients. Otherwise, botanical products containing isoflavones from soy bean or red clover have great variability in bioavailability, have a broader spectrum of action than estradiol, and have predominant estrogen receptor-b activity. The efficacy of phytoestrogens on VMS is similar to placebo. They should be avoided in women with breast cancer and, in particular, in women being treated with tamoxifen or aromatase inhibitors due to possible antagonism. Cimicifuga racemosa is not a phytoestrogen, has partial serotonin agonist action and has a modest effect on VMS. CONCLUSIONS: There are safe non-hormonal conventional treatments for menopausal VMS, although they are less efficacious than estrogens. The indication of phytochemicals is for women who make this choice on personal beliefs; long-term studies of larger groups of patients are needed to assess safety.

Menopausal hot flushes and night sweats: where are we now?

OBJECTIVE: An overview of the current knowledge on the etiology and treatment of vasomotor symptoms in postmenopausal women. MATERIALS AND METHODS: Acknowledged experts in the field contributed a brief assessment of their areas of interest which were combined and edited into the final manuscript. RESULTS: Women around the world experience vasomotor symptoms as they enter and complete the menopause transition. Vasomotor symptoms, specifically hot flushes, are caused by a narrowing of the thermoneutral zone in the brain. This effect, although related to estrogen withdrawal, is most likely related to changes in central nervous system neurotransmitters. Peripheral vascular reactivity is also altered in symptomatic women. Estrogen replacement therapy is the most effective treatment for hot flushes. Of the other interventions investigated, selective serotonin and selective norepinephrine reuptake inhibitors and gabapentin show efficacy greater than placebo. Objective monitoring of hot flushes indicates a robust improvement with hormone replacement therapy but little to no change with placebo. These data suggest that the subjective assessment of responses to therapy for vasomotor symptom results in inaccurate data. Hot flushes have recently been associated with increased cardiovascular risks and a lower incidence of breast cancer, but these data require confirmation. CONCLUSIONS: Vasomotor symptoms are experienced by women of all ethnic groups. They are caused by changes in the central nervous system associated with estrogen withdrawal and are best treated with estrogen replacement therapy. Objective monitoring of hot flushes indicates that placebo has little to no effect on their improvement. Subjective assessments of hot flushes in clinical trials may be inaccurate based on objective measurement of the frequency of hot flushes. Based on preliminary reports, women experiencing hot flushes have an increased risk of cardiovascular disease and a reduced incidence of breast cancer.

Age of menopause and impact of climacteric symptoms by geographical region.

OBJECTIVE: To describe differences in the age of onset of menopause and in the prevalence of climacteric symptoms in different geographical areas. DESIGN: Systematic review of published data on onset of menopause and symptoms in Europe, North America, Latin America and Asia. METHODS: We identified publications by searching electronic databases, including MEDLINE (1966-October 2009) and EMBASE (1975-October 2009). Primary search criteria were age of menopause and climacteric symptoms. A sensitive analysis that excluded papers without full data was performed. RESULTS: The median age at menopause in Europe ranges from 50.1 to 52.8 years, in North America from 50.5 to 51.4 years, in Latin America from 43.8 to 53 years, and in Asia from 42.1 to 49.5 years. The frequency of vasomotor symptoms varies widely depending on the geographical region, selection of criteria, and method of symptom identification. The prevalence of such symptoms ranges from 74% of women in Europe, 36-50% in North America, 45-69% in Latin America and 22-63% in Asia, as reported in different, large, epidemiological studies. CONCLUSION: There are wide geographical differences in the prevalence of menopausal symptomatology and some differences in the age of onset of menopause. Both in Asia and Latin America, women of poorer socioeconomic status have significantly earlier onset of menopause. Within a geographical region, there are ethnic differences in menopause symptoms. Given differences in study methodologies, firm conclusions are not possible. However, regional differences in age at menopause and in climacteric symptoms are important to acknowledge and lay the foundation for an informed approach to the management of menopause and an understanding of its impact on women's health in the different regions of the world.

Ethinylestradiol/cyproterone acetate in polycystic ovary syndrome: lipid and carbohydrate changes.

OBJECTIVE: Ethinylestradiol (EE) combined with the antiandrogenic progestin cyproterone acetate (CPA) is a possible treatment in polycystic ovary syndrome (PCOS). We investigated the impact of EE/CPA on lipid and carbohydrate metabolism in women with PCOS,who were otherwise healthy. METHOD: The 31 women were separated into two groups paired by body mass index (BMI): Group A (control, n = 15) were cycled with 10 mg medroxyprogesterone acetate (MPA) x 10 days (Provera, Pharmacia & Upjohn) every month for 3 months; Group B (n = 16) were treated with 35 microg EE/2 mg CPA (Diane 35, Schering) for 3 months. Metabolic and hormonal conditions were similar in both groups. RESULTS: Group A showed no change in any hormone or metabolic parameter. Group B showed a significant decrease in free androgen index (-81%) and increase in sex hormone binding globulin (+ 639%), a decrease in low density lipoprotein cholesterol (-14%) and total cholesterol/high density lipoprotein (HDL) cholesterol index (-19%), and increases in HDL cholesterol (+ 23%) and triglycerides (+ 82%) (p < 0.001). Fasting insulin increased in 18%, the glucose/insulin index worsened in 8%, and the plasma glucose disappearance worsened in 12%, with no statistical significance (p= 0.092, p=0.308 and p= 0.237, respectively). CONCLUSION: Treatment of PCOS with EE/CPA induces important favorable changes regarding hormone parameters associated with hyperandrogenism, significant favorable changes in lipid profile except for triglyceride increase, and no significant change in carbohydrate metabolism (measured by fasting insulin, glucose/insulin index and plasma glucose disappearance). MPA cycling does not change any of these parameters.

Phytoestrogens possess a weak antioxidant activity on low density lipoprotein in contrast to the flavonoid quercetin in vitro in postmenopausal women.

BACKGROUND: Phytoestrogens are a family of plant-derived compounds with weak estrogenic and antiestrogenic properties. The antioxidant capacity of phytoestrogens has been proposed as one of the important mechanisms that explain their health benefits. OBJECTIVE: To determine the in vitro potency of three phytoestrogens, ubiquitous in food, (biochanin A, daidzein and genistein) as antioxidants of low density lipoprotein (LDL) and to compare them with the well-established antioxidant actions of estradiol and quercetin, an ubiquitous flavonoid which is found in high concentration in onions, tea and berries. METHODS: LDL was isolated by ultracentrifugation from the plasma of ten healthy postmenopausal women who were not on hormone therapy. Aliquots containing 0.5 mg of protein were incubated for 4 h with CuSO4 15 micromol/l to induce oxidative stress and with one of the five compounds studied: estradiol, quercetin, biochanin A, daidzein, and genistein, in doses of 0, 5, 15, 50, 500, 1000 and 2000 micromol/l. In addition, we studied the combined effect of estradiol 1 micromol/l plus quercetin 1 micromol/l, comparing their antioxidant action with that of each compound separately. Malonaldehyde (MDE nmol/ mg protein) was measured as a marker of LDL oxidation. RESULTS: Estradiol and quercetin induced a dose-dependent decrease in MDE concentration (p < 0.01). Comparing the areas under the curve, the antioxidant effect of quercetin was 8 times higher than the one observed with estradiol (p < 0.01). A 50% decrease in MDE was reached by quercetin at a concentration of 3.4 micromol/l, estradiol at 29 micromol/l, genistein at 280 micromol/l, biochanin at 1312 mmol/l and daidzein at 8007 mmol/l. Estradiol 1 micromol/l and quercetin 1 micromol/l did not modify MDE generation separately, but, when incubated combined, there was a significant decrease of MDE (p < 0.02). CONCLUSION: The phytoestrogens studied showed a weak antioxidant activity in vitro. The flavonoid quercetin, in contrast, showed the most potent antioxidant activity in vitro, higher than estradiol. Estradiol and quercetin showed additive antioxidant activity. We speculate that different compounds with variable antioxidant effects could amplify their antioxidant capacity when acting combined.

The effect of 17beta-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of gamma-tocopherol and melatonin.

OBJECTIVE: Estrogens have a potent antioxidant effect on low-density lipoprotein (LDL) cholesterol in vitro and in vivo. A variety of compounds with antioxidant properties, such as vitamins and other hormones, also have been recommended in clinical practice to prevent several diseases related to oxidation. The aim of this study was to compare the antioxidant potency of estradiol (E2), the liposoluble vitamin E (both, alpha- and gamma-tocopherol), and melatonin. DESIGN: LDL was isolated by ultracentrifugation from the plasma of 11 healthy, untreated postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with 15 microM of CuSO4 to induce oxidative stress and with one of the four compounds studied: E2, alpha-tocopherol, gamma-tocopherol, or melatonin in doses of 0, 5, 15, 50, and 500 microM and 1 and 2 mM. Malondialdehyde (MDA) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration (nmol/mg protein). MDA values were significantly different as compared with baseline at 5 microM of E2 (F = 47.17; p < 0.0001). Alpha-tocopherol, gamma-tocopherol, and melatonin also showed a significant decrease in MDA concentration but to a lesser degree. The reduction of MDA reached statistical significance at 50 microM with alpha-tocopherol, 500 microM with melatonin, and 1 mM with gamma-tocopherol. The antioxidant effect also reached a plateau at concentrations of 50 microM of E2 and 1 mM of alpha-tocopherol; gamma-tocopherol and melatonin did not reach a plateau at any dose tested. CONCLUSIONS: The antioxidant potency of E2 in vitro is at least 10-100 times greater than alpha- and gamma-tocopherol and melatonin. Whether this finding implies a better performance of E2 as a protective agent against oxidation-related diseases remains to be determined.

Natural infections of Leishmania peruviana in animals in the Peruvian Andes.

Evidence that domestic dogs may act as reservoir hosts for cutaneous leishmaniasis in the Peruvian Andes is provided by the isolation, for the first time, from naturally infected dogs of parasites identified (by isoenzymes) as Leishmania peruviana. Leishmania parasites were isolated from nasal aspirates or biopsies from 5 (1.8%) of 279 asymptomatic dogs samples in endemic villages of the Peruvian Andes. In addition, Leishmania (Viannia) infections were identified in 15 (5.4%) of 276 nasal samples by the polymerase chain reaction (PCR) using subgenus-specific primers. Further circumstantial evidence for a reservoir role for dogs comes from the finding of a relatively high dog blood index among the sandfly vectors collected inside houses (29% for Lutzomyia peruensis and 17% for Lu. verrucarum). Possible wild mammal reservoir hosts for Andean cutaneous leishmaniasis were also detected in endemic villages. At least 8 species were identified among the 1266 small mammals trapped. Leishmania parasites were isolated from blood or skin biopsies taken from 2 (2.6%) of 78 Didelphis albiventris and 6 (1.2%) of 511 Phyllotis andinum. Three isolates were identified by isoenzymes as L. peruviana, and the other 5 were identified by PCR as Leishmania (Viannia) species. Leishmania (Viannia) infections were also identified by PCR directly on skin biopsies taken from 2 (2.8%) of 72 D. albiventris, 1 (0.2%) of 499 P. andinum, and 4 (2.6%) of 153 Akodon sp.

An outbreak of acute bartonellosis (Oroya fever) in the Urubamba region of Peru, 1998.

During May 1998, we conducted a case-control study of 357 participants from 60 households during an outbreak of acute bartonellosis in the Urubamba Valley, Peru, a region not previously considered endemic for this disease. Blood and insect specimens were collected and environmental assessments were done. Case-patients (n = 22) were defined by fever, anemia, and intra-erythrocytic coccobacilli seen in thin smears. Most case-patients were children (median age = 6.5 years). Case-patients more frequently reported sand fly bites than individuals of neighboring households (odds ratio [OR] = 5.8, 95% confidence interval [CI] = 1.2-39.2), or members from randomly selected households > or = 5 km away (OR = 8.5, 95% CI = 1.7-57.9). Bartonella bacilliformis isolated from blood was confirmed by nucleotide sequencing (citrate synthase [g/tA], 338 basepairs). Using bacterial isolation (n = 141) as the standard, sensitivity, specificity, and positive predictive value of thin smears were 36%, 96%, and 44%, respectively. Patients with clinical syndromes compatible with bartonellosis should be treated with appropriate antibiotics regardless of thin-smear results.

Importancia de la Lutzomia peruensis en la transmisión de la enfermedad de Carrión en el Valle Sagrado de los incas. Urubamba Cusco, Perú / Importance of Lutzomyia peruensis in the transmission of the Carrionïs disease in the Incaïs Sacred Valley. Urubamba Cusco, Peru

En el valle Sagrado de los Incas (Valle del Río Urubamba) encontramos una sola de Lutzomyia, nos referimos a la Lutzomyia suele compartir su habitat con el vector de la enfermedad de Carrión, la Lutzomyia verrucarum. Los aspectos entomológicos fueron levados a cabo, en Mayo de 1998. Las colectas entomológicas se realizaron utilizando trampas de luz CDC toda la noche y en capturas diurnas en las viviendas.Se muestra la importancia de Lutzomyia peruensis incriminándola epidemiológicamente y se detectó Bartonella bacilliformis mediante PCR y haciendo secuenciamiento de ADN. Se presenta también la estimación del riesgo entomólogico de transmisión de bartonelosis por Lutzomyia peruensis, mediante el índice de inoculación de Bartonella bacilliformis

[Comparison of the antioxidant effect of estriol and estradiol on low density lipoproteins in post-menopausal women]. / Comparación de la acción antioxidante de estriol y estradiol in vitro sobre lipoproteínas de baja densidad en mujeres postmenopáusicas.

BACKGROUND: Estradiol (E2) has a potent antioxidant effect on low density lipoproteins (LDL) in vitro and in vivo, which could be important in explaining the cardioprotective effect of hormone replacement therapy (HRT) in post menopausal women. Estriol (E3), on the other hand, is a weak estrogen with low metabolic effects on different tissues, and at present no cardioprotective effect has been attributed to this steroid. AIM: To study the antioxidant effect of E3 on LDL and to compare it with the potent antioxidant action exhibited by E2. SUBJECTS AND METHODS: After LDL was isolated by ultra centrifugation from plasma of 12 healthy untreated post menopausal women, it was divided into aliquots containing 0.5 mg of LDL protein. Estriol and E2 in doses of 0, 1, 5, 15 and 50 microM were incubated with different aliquots of LDL. CuSO4 15 microM was added to each aliquot to induce an oxidative stress. The aliquots were then incubated during 4 hours at 37 degrees C. Malonaldehyde (MDA) was measured as a marker of LDL oxidation, and expressed as nM/mg protein. RESULTS: (mean +/- SD): Estriol induced a dose-dependent decrease in MDA concentration (baseline 62.8 +/- 21.7; 1 microM: 61.5 +/- 23.0; 5 microM: 52.9 +/- 20.3; 15 microM 43.5 +/- 20.1 and 50 microM: 31.0 +/- 17.6 nM/mg protein; F = 92.4; p < 0.0001), reaching a mean decrease of 50.7% at the highest dose tested. Estradiol has a similar dose-dependent decrease in MDA concentration (F = 60.2; p < 0.0001), revealing a more potent effect than E3 (p < 0.05), with a mean decrease of 67.4% at the highest dose tested. CONCLUSIONS: Our results demonstrate that estriol shows an important antioxidant action of LDL in vitro, although its effect is less potent than estradiol. These results raise the possibility that estriol could have a cardioprotective effect in post menopausal women, possibility that has not been yet demonstrated.

In vitro effect of estradiol, progesterone, testosterone, and of combined estradiol/progestins on low density lipoprotein (LDL) oxidation in postmenopausal women.

OBJECTIVE: One of the mechanisms currently proposed to explain the cardioprotective effect of hormone replacement therapy (HRT) is the antioxidative property of estrogens. Considering that HRT involves the administration of an estrogen, usually combined with a progestin and sometimes with an androgen, we investigated the following in vitro: (1) the effect of estradiol, progesterone, and testosterone on the oxidation of low density lipoprotein; (2) the possible pro-oxidative effect of progesterone and testosterone on native low density lipoprotein; and (3) the possible modification of the antioxidant effect of estradiol on low density lipoprotein induced by progestins. DESIGN: Low density lipoprotein was isolated from blood samples obtained from 20 untreated postmenopausal women and divided in multiple aliquots, each containing 0.5 mg LDL protein. In Protocol 1 (n = 10) different doses of estradiol, progesterone, and testosterone ranging from 0 to 26 micrograms/ml were tested inducing oxidation with 15 microM copper sulfate. In Protocol 2 (n = 6) we studied the rate of oxidation of low density lipoprotein incubated with progesterone or testosterone without any oxidative induction. In Protocol 3 (n = 10) we studied the concomitant effect of 15 microM estradiol with four separate progestins (progesterone, medroxyprogesterone acetate, norethindrone, and norgestrel) in different doses (0, 5, 15, and 50 microM). After incubation for 4 h at 37 degrees C, malonaldehyde was measured as a marker of low density lipoprotein oxidation. The results were expressed in mean +/- SD. RESULTS: Protocol 1: Estradiol induced a dose-dependent decrease in malonaldehyde generation, from a baseline of 61.8 +/- 30.2 nmol/mg protein to 11.6 +/- 7.1 nmol/mg protein at the highest dose of estradiol tested (p < 0.0001). Progesterone or testosterone did not modify malonaldehyde generation. Protocol 2: Progesterone and testosterone did not show pro-oxidative action. Protocol 3: Estradiol 15 microM alone induced a 35% decrease in malonaldehyde generation, from a baseline of 75.4 +/- 25.4 to 49.3 +/- 18.8 nmol/mg protein (p < 0.0001). Norgestrel and norethindrone did not modify the antioxidant effect of estradiol (p > 0.05). Progesterone and medroxyprogesterone acetate induced a further reduction of malonaldehyde concentration to 37.2 +/- 20.8 and 38.6 +/- 18.2 nmol/mg protein, only at the highest dose tested (p < 0.02 and p < 0.01, respectively). CONCLUSIONS: Our results demonstrate that, in contrast with the potent antioxidant effect of estradiol, progesterone and testosterone did not show any pro- or antioxidant effect on low density lipoprotein in vitro. Furthermore, progestins did not counteract the antioxidant effect of estradiol in vitro.

Pharmacokinetic comparison between Conpremin (Premarin) and a generic preparation of conjugated estrogens.

OBJECTIVES: To determine the relative bioavailability of the estrogenic components of a generic brand of conjugated estrogens marketed in Chile in comparison to that of Conpremin (Premarin in the United States). METHODS: A randomized cross-over study was conducted on 16 healthy postmenopausal women receiving single oral doses of either two Conpremin 0.625-mg tablets or two 0.625-mg tablets of the generic brand, with a 14-day wash-out interval between doses. A gas chromatography tandem mass spectrometry assay was used to determine estrogen components. RESULTS: The peak plasma concentrations of unconjugated and total estrone and equilin, unconjugated 17 beta-dihydroequilin and 17 beta-estradiol were higher and occurred earlier with the generic conjugated estrogens than with Conpremin. The 90% confidence limits for both variables lay outside the accepted bioequivalence limits of 80-125%. Additionally, no measurable plasma concentration of unconjugated delta 8,9-dehydroestrone or 17 beta-delta 8,9-dehydroestradiol was seen after administration of the generic conjugated estrogens. CONCLUSIONS: These pharmacokinetic results indicate that the generic tablets do not have the modified-release characteristics of Conpremin tablets. In addition, the absence of delta 8,9-dehydroestrone and 17 beta-delta 8,9-dehydroestradiol in the plasma indicates that the generic form is not compositionally equivalent to Conpremin.

Cutaneous leishmaniasis in the Peruvian Andes: risk factors identified from a village cohort study.

Risk factors for cutaneous leishmaniasis were identified from a comparative study of transmission rates in 27 villages in the Departments of Lima, Ancash, and Piura in Peru. To evaluate regression analysis as a tool for the incrimination of sand fly vectors in the absence of other biologic evidence, univariate and multivariate logistic regression analyses were used to identify which of 14 variables (the abundance of nine sand fly species, four social factors, and region) predicted transmission rates in villages (incidence, active prevalence, or cumulative prevalence). In general, suspected or proven vectors (e.g., Lutzomyia peruensis) had the strongest associations with transmission rate, indicating that regression is a useful supplementary method of incriminating vectors. Regression was then used to quantify the importance of suspected risk factors. Transmission rate increased with the abundance of Lu. peruensis, Lu. ayacuchensis, Lu. noguchii, and, to a lesser extent, Lu. verrucarum and transmission was higher among villagers who slept more frequently in temporary shelters in crop areas. There were also weak effects of the number of dogs/ person (negative) and the number of persons/household (positive). Linear regressions failed to detect a threshold sand fly density below which transmission ceases. The minimal adequate multiple regression model explained 82% of the variance in village incidence rates. This model was used to predict the effect on incidence of reducing each of the four suspected vectors in northern and southern Peru. The results indicate that vector control programs in the south should aim at Lu. peruensis, Lu. verrucarum, and Lu. noguchii, but focus on Lu. ayacuchensis in the north.

[Effects of hormone replacement therapy in bone resorption, in post-menopausal women]. / Modificación de la reabsorción ósea con terapia hormonal de reemplazo en la postmenopausia.

BACKGROUND: The effects of different therapies on bone loss rate can be measured using biochemical markers of bone resorption such as urinary hydroxyproline. AIM: To study the effects of hormone replacement therapy on urinary hydroxyproline in postmenopausal women. PATIENTS AND METHODS: Eighty three postmenopausal women without hormone replacement therapy, 54 postmenopausal women receiving hormone replacement therapy and 16 premenopausal women (considered as the control group) were studied. Hydroxyproline was measured in an early morning urine sample, after one day of diet without meat or gelatin. RESULTS: Urinary hydroxyproline in premenopausal women was 33.7 +/- 7.9 mg/g creatinine. The figure for postmenopausal women with hormonal replacement therapy was 33.7 +/- 5.9 mg/g creatinine. Postmenopausal women without replacement therapy had an urinary hydroxyproline of 47.4 +/- 8.5 mg/g creatinine, significantly higher than that of premenopausal and supplemented women. In 21 postmenopausal women, hydroxyproline was measured before and after three months of replacement therapy, values decreased 35.5 +/- 11% in this period and there was a direct correlation between initial values and the degree of reduction (r = 0.69, p < 0.001). CONCLUSIONS: Postmenopausal women receiving hormone replacement therapy have a urinary hydroxyproline excretion similar to that of premenopausal women.