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Biomedical subjects

Rogerio A Lobo

Publications and source records attributed to Rogerio A Lobo.

At least 19 recordsLinked to original sources

A comparison of oral and transdermal short-term estrogen therapy in postmenopausal women with metabolic syndrome.

OBJECTIVE: To determine whether it would be preferable to prescribe oral or transdermal estrogen to symptomatic postmenopausal women with metabolic syndrome (MBS). DESIGN: Prospective, randomized study. SETTING: Academic medical center. PATIENT(S): Fifty obese postmenopausal women with MBS. INTERVENTION(S): Women were randomized to receive either oral E(2) (oE(2), 1 mg/d) or transdermal E(2) (tE(2), 0.05 mg/d) for 3 months. Fasting blood was obtained before and after treatment for glucose, insulin, lipid profiles, the adipocytokines (adiponectin, leptin, and resistin), and a gastric peptide (ghrelin). In addition, a 75-g 2-hour oral glucose-tolerance and intravenous insulin-tolerance tests were performed before and after E(2). MAIN OUTCOME MEASURE(S): Changes in parameters of insulin resistance (IR), lipid profiles, and adipocytokine levels. RESULT(S): Mean serum concentrations of E(2) in women using oE(2) and tE(2) were 39.1 +/- 5.6 and 49.2 +/- 28.6 pg/mL, respectively. After oE(2), there was a statistically significant worsening of IR markers, including an increase in baseline insulin (15.28 +/- 1.27 to 22.02 +/- 2.40 microU/mL), a reduction in quantitative insulin-sensitivity check index (0.3177 +/- 0.0043 to 0.2977 +/- 0.0057), and an increase in homeostasis model assessment (3.96 +/- 0.38 to 8.59 +/- 2.08). The only significant change in the lipid profile was an increase in high-density-lipoprotein cholesterol (50.46 +/- 2.34 vs. 55.08 +/- 2.51 mg/dL). Leptin levels increased (81.43 +/- 7.87 ng/mL to 94.10 +/- 6.56 ng/mL), and adiponectin decreased nonsignificantly, resulting in an increased leptin-adiponectin ratio (12.56 +/- 1.70 to 15.86 +/- 2.24); resistin levels increased (9.37 +/- 1.09 ng/mL to 11.72 +/- 1.10 ng/mL); and baseline ghrelin levels decreased (701.64 +/- 59.79 pg/mL to 581.72 +/- 36.07 pg/mL). After tE(2), no significant changes in IR parameters occurred, except for a decrease in glucose-insulin ratio. There were no changes in lipid parameters. Leptin did not change (72.7 +/- 9.3 ng/mL to 78.8 +/- 7.9 ng/mL), whereas adiponectin levels showed statistically significant increase (7.97 +/- 0.7 microg/mL vs. 9.96 +/- 1.1 microg/mL), with no change in the leptin-adiponectin ratio. Resistin levels did not change significantly, and ghrelin levels decreased (888.52 +/- 109.98 pg/mL vs. 579.04 +/- 39.30 pg/mL). CONCLUSION(S): This short-term study suggests that oral E(2) may worsen IR and adipocytokine parameters, worsening cardiovascular risk. Transdermal E(2) had minimal effects on IR and resulted in higher adiponectin. Although these data may not reflect alterations that occur with estrogen therapy in more metabolically normal postmenopausal women or with longer term therapy, the findings suggest that tE(2) may be a preferable treatment for obese women with MBS. Long-term studies are needed to make any recommendations.

Administration, Cutaneous↗

Elevated serum müllerian-inhibiting substance may be a marker for ovarian hyperstimulation syndrome in normal women undergoing in vitro fertilization.

We identified patients who experienced ovarian hyperstimulation syndrome (OHSS) (n = 16) and compared their baseline pretreatment levels of müllerian-inhibiting substance (MIS) to age- and weight-matched patients with normal responses to gonadotropins (n = 14). Baseline serum MIS in patients with OHSS were sixfold higher than those seen in normal controls (3.62 +/- 0.87 vs. 0.63 +/- 0.09 ng/mL; P=.0036), indicating that MIS could potentially serve as a useful marker for identifying patients at risk for OHSS.

Adult↗

Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin.

OBJECTIVE: Metabolic syndrome (MBS) is a significant health care problem in postmenopausal women and is driven largely by obesity. We wished to assess the prevalence of insulin resistance (IR), diagnosed using practical methods, and whether several adipocyte factors (adiponectin, leptin, resistin) or the gastric peptide ghrelin, associated with cardiovascular risk, might be abnormal and may relate to IR. STUDY DESIGN: We evaluated 37 obese postmenopausal women with MBS and 34 matched obese premenopausal controls, as well as 14 non-obese premenopausal controls. We measured fasting glucose and insulin, performed 75 g 2 hr oral glucose tolerance and intravenous insulin tolerance tests to assess IR, and measured fasting lipids, adiponectin, leptin, resistin and ghrelin. RESULTS: The kinetic decline in glucose after insulin (kITT) as a marker of IR was the most frequently abnormal test (abnormal in 81%), with QUICKI, HOMA, and a modification of the Matsuda-DeFronzo index (ISIM) abnormal in 76, 73, and 68%, respectively. The GIR was abnormal in only 35% of subjects. Leptin and resistin were elevated and adiponectin and ghrelin were decreased in the postmenopausal women, compared to both groups of premenopausal controls. BMI correlated strongly with markers of insulin resistance as well as adipocytokine values. After controlling for BMI, only leptin was predictive of ISIM. CONCLUSION: Being overweight after menopause results in worsening IR and elevations in adipocytokine levels. While BMI is the most important factor, abnormal adipocytokine secretion may enhance IR and increase cardiovascular risk in postmenopausal women.

Adiponectin↗

Endothelial dysfunction in PCOS: role of obesity and adipose hormones.

PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found. This study was designed to determine if abnormal carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age: 25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT, brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and resistin were measured. RESULTS: PCOS, IMT was increased (P <.01), FMD was decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05), whereas leptin and resistin were not different compared with matched controls. Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and QUICKI correlated positively and negatively with IMT (P <.01). There was a significant negative correlation between adiponectin and IMT (P <.05). These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters. CONCLUSIONS: These data suggest that young women with PCOS have evidence for altered endothelial function. Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin. Both insulin resistance and adiponectin appear to be important parameters. It is hypothesized that the type of fat distribution may influence these factors.

Adipocytes↗

Should symptomatic menopausal women be offered hormone therapy?

UNLABELLED: Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.

Aged↗

Postmenopausal oral estrogen therapy and blood pressure in normotensive and hypertensive subjects: the Estrogen in the Prevention of Atherosclerosis Trial.

OBJECTIVE: To determine if 17beta-estradiol increases blood pressure in postmenopausal women. DESIGN: A total of 222 healthy postmenopausal women were randomly assigned to either 1 mg micronized 17beta-estradiol daily or placebo for 2 years. Blood pressure measurements were obtained every other month and common carotid artery intima-media thickness measured every 6 months. Statistical analyses comparing longitudinal changes in systolic and diastolic blood pressure between treatment groups used a mixed general linear model including interaction terms to evaluate variations by age or estradiol level. RESULTS: Both placebo and estradiol groups showed small declines in systolic and diastolic blood pressure during the trial among the normotensive subjects and subjects on antihypertensive medications. However, the decline did not differ significantly between the groups. Treatment effects on systolic blood pressure differed significantly by the age of the subject (interaction P value = 0.04) with younger women on estradiol showing on average a rise in systolic blood pressure, and older women a decline. The association between serum estradiol level and systolic blood pressure showed a similar modification with age (P = 0.03). Changes in systolic blood pressure in women on estradiol were positively correlated with intima-media thickness progression (P = 0.03). CONCLUSIONS: Overall, 17beta-estradiol did not influence changes in blood pressure in normotensive or hypertensive women. The effect of 17beta-estradiol treatment on systolic blood pressure may be influenced by a woman's age. Estradiol may increase systolic blood pressure in younger postmenopausal women, while having the opposite effect in older postmenopausal women.

Age Factors↗

Appropriate use of hormones should alleviate concerns of cardiovascular and breast cancer risk.

Since the publication of several recent randomized trials in the United States, prescriptions for hormonal therapy have dropped precipitously. This has been due, in large part, to the concerns about the increased risk of cardiovascular (CV) disease and breast cancer among the hormone users. This review takes the perspective that the appropriate use of hormones largely alleviates these concerns. The appropriate use of hormones pertains to treating younger, healthy women who have menopausal symptoms as well as using low-doses of hormones. In the randomized trials, suggesting an increased CV risk, the older women were largely asymptomatic and had other CV risk factors. Data are presented to suggest that there is no increased CV risk with hormonal therapy in younger, healthy women within 5 years of menopause. Moreover, a model is presented to attempt to explain the potential of preventing CV disease when estrogen is begun early, and the relative hazard associated with later use. The risk of breast cancer with hormonal therapy is put into perspective with the realization that this risk is related to hormonal dose and duration of use, and that the absolute risk remains small. Use of progestogens, in particular, appears to enhance this risk. The appropriate use of hormones also pertains to using lower-doses. Here data are presented showing efficacy with lower-doses and improved safety. With the use of lower-doses of estrogens, the progestogen dose, as required in women with a uterus, can be minimized.

Adult↗

Ovarian size and blood flow in women with polycystic ovary syndrome and their correlations with endocrine parameters.

OBJECTIVE: To determine how common polycystic ovarian morphology may be in women given the clinical diagnosis of polycystic ovary syndrome (PCOS) based on chronic anovulation and hyperandrogenism and whether certain hormonal factors correlate with ovarian morphology and blood flow. DESIGN: Prospective study. SETTING: Two academic endocrinology centers in Italy. PATIENT(S): Three hundred twenty-six women with PCOS and 50 age-matched and weight-matched ovulatory women. INTERVENTION(S): Ultrasound assessment of ovarian morphology in patients and controls and ovarian blood flow and fasting hormone levels in a subset of 50 patients and matched controls. MAIN OUTCOME MEASURE(S): Ovarian morphological assessments, ovarian blood flow by pulsatility index (PI) and resistance index (RI), and measurements of gonadotropins, estrogen, sex hormone-binding globulin, androgens, inhibin B, glucose, and insulin. RESULT(S): Using strict ultrasound criteria, 195 woman (60%) had enlarged ovaries, 135 (35%) had normal ovarian size but characteristic morphology, and 16 (5%) had normal size and morphology. Ovarian blood flow was increased (reduced PI and RI) in PCOS. All hormonal parameters were elevated in PCOS. Ovarian size correlated only with insulin and a measure of insulin resistance. Ovarian blood flow correlated positively with insulin, T, free T, and E2 but not with luteinizing hormone. Inhibin B showed a negative correlation with ovarian blood flow. CONCLUSION(S): When a clinical diagnosis of PCOS was made, virtually all women were found to have characteristic ovarian morphology. Insulin correlated with increased ovarian size as well as with increased blood flow. Blood flow also correlated positively with sex steroids but negatively with inhibin B.

Analysis of Variance↗

Müllerian-inhibiting substance reflects ovarian findings in women with polycystic ovary syndrome better than does inhibin B.

OBJECTIVE: To investigate Müllerian-inhibiting substance (MIS) levels in women with polycystic ovary syndrome (PCOS), as well as relationships to ovarian morphology, levels of inhibin B, and other reproductive hormones. DESIGN: Prospective clinical study. SETTING: Academic endocrinology centers in Palermo, Italy and New York. PATIENT(S): Forty-six women with PCOS, recruited on the basis of the classic criteria of chronic anovulation and hyperandrogenism, and 25 age-matched ovulatory controls. INTERVENTION(S): Fasting blood was obtained in all subjects in the early follicular phase (days 5-6) after spontaneous or induced menses (in PCOS), and transvaginal ultrasounds were performed. MAIN OUTCOME MEASURE(S): Assessment of values for luteinizing hormone (LH), testosterone (T), androstenedione (A), estradiol (E2), inhibin B, MIS, fasting insulin, and the calculated quantitative sensitivity check index (QUICKI), as well as assessments of ovarian volume and blood flow. RESULT(S): Women with PCOS had higher LH, T, and A; higher insulin and lower QUICKI; and higher ovarian volume and lower pulsatility index. Inhibin B concentrations were statistically significantly higher in PCOS patients (70 +/- 8.0 vs. 40 +/- 3.4 pg/mL), as was MIS (6.7 +/- 0.9 vs. 4.6 +/- 0.5 ng/mL). Inhibin B had a statistically significant direct correlation with levels of MIS (r = 0.351). However, MIS, but not inhibin B, had a statistically significant positive correlation with ovarian size (r = 0.350); the reproductive hormones LH, T, A, and E2; and insulin (r = 0.249), independent of body mass index. Women with PCOS with the highest levels of MIS had higher ovarian volumes and values of LH, T, A, and insulin. CONCLUSION(S): Measurements of MIS reflect ovarian findings in PCOS better than levels of inhibin B and are more frequently elevated. However, MIS lacks sensitivity for use as a diagnostic tool in PCOS.

Anovulation↗

Transdermal drug delivery: clinical considerations for the obstetrician-gynecologist.

INTRODUCTION: The first transdermal drug delivery system was introduced in the United States over 20 years ago. Created as an alternative route of administration to improve patient compliance as well as to reduce side effects, the transdermal delivery of drugs now represents a $1.5 to $2 billion market and is growing rapidly. DATA SOURCES: The medical literature from 1980 to 2005 was searched using the PubMed search engine. The search term was "transdermal," limited to human clinical trials. Abstracts were used to identify clinical trials that compared transdermal preparations and their oral counterparts in the same study. TABULATION, INTEGRATION, AND RESULTS: In this article, we review the rationale for the transdermal administration of drugs; discuss aspects of the anatomy and physiology of the skin relevant to drug transport; examine the qualities required for a drug to be a good candidate for transdermal delivery; and consider key principles for the evaluation of the relative benefits of transdermal delivery, using studies of hormone replacement therapy and oral contraceptive as examples. CONCLUSION: The data reviewed here suggest that certain clinical situations support the use of the transdermal administration of drugs over their oral counterparts.

Administration, Cutaneous↗

A short study in the treatment of hot flashes with buccal administration of 17-beta estradiol.

OBJECTIVE: To assess the efficacy and safety of 17-beta estradiol buccal tablets in reducing hot flush frequency (HFF) in postmenopausal women. METHODS: Estradiol buccal tablets containing 0.05, 0.1, 0.2, or 0.4 mg or placebo were administered for 28 days to 99 postmenopausal women in a randomized, double-blind study; 19 premenopausal women were studied concurrently for comparison of laboratory data. Objective and subjective assessments of HFF were obtained along with measures of estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS: Measurements of HFF revealed significant decreases from baseline in all estradiol groups (P < 0.01). In the 0.4 mg group, HFF decreased significantly compared to placebo (P < 0.01). All estradiol doses produced similar improvement in the vaginal maturation index. Mean serum estradiol levels increased as doses increased but were lower than in the premenopausal subjects. Mean serum FSH and LH levels decreased in all estradiol groups but not to the levels of the premenopausal subjects; the greatest decrease occurred at the two highest estradiol doses. CONCLUSION: A numerical dose-response relationship with hot flushes was seen in this pilot study comparing 0.05, 0.1, 0.2, and 0.4 mg buccal estradiol. Only 0.4 mg 17-beta estradiol significantly reduced the occurrence of hot flushes compared to placebo.

Administration, Buccal↗

Does metformin induce ovulation in normoandrogenic anovulatory women?

OBJECTIVE: This study was undertaken to evaluate the efficacy of metformin in women with anovulation who do not have evidence for hyperandrogenism and classic polycystic ovary syndrome. STUDY DESIGN: A randomized trial of metformin (1500 mg daily) and placebo in 24 anovulatory women was undertaken for 3 months. Assessments of changes in hormone levels and insulin sensitivity were carried out. Abnormal hormonal values were defined by levels exceeding the range in normal ovulatory controls. RESULTS: Anovulatory women had normal androgen levels and luteinizing hormone but had higher serum insulin and lower insulin sensitivity compared with controls. Over 3 months, there were 16 ovulatory cycles with metformin and only 4 with placebo ( P < .05). Success of ovulation did not correlate with changes in androgen, insulin, or insulin sensitivity parameters. CONCLUSION: Metformin may be useful for inducing ovulation in anovulatory women who do not have hyperandrogenism. This effect may be independent of a lowering of androgen or insulin levels.

Adult↗

Areas for future inquiry.

Osteoporosis, heart disease, and cancer remain worldwide challenges for women's health. This article discusses areas for future inquiry in these areas of research.

Cardiovascular Diseases↗

Elevated subclinical atherosclerosis associated with oophorectomy is related to time since menopause rather than type of menopause.

OBJECTIVE: To compare common carotid artery intima-media thickness (IMT) between women who had natural menopause with those who had surgical menopause and to correlate IMT with time since menopause. DESIGN: Cross-sectional study. SETTING: University-based research clinic. PATIENT(S): One hundred eighty-nine healthy postmenopausal women who were not on hormone therapy (HT), age 46 to 81 (n = 132, women who did not have a prior hysterectomy or oophorectomy; n = 57, women who had undergone hysterectomy with bilateral oophorectomy). INTERVENTION(S): B-mode ultrasonography of the carotid artery, standardized questionnaires, and fasting blood samples were completed to evaluate the relationship between type of menopause, time since menopause, and subclinical atherosclerosis. MAIN OUTCOME MEASURE(S): Carotid artery IMT. RESULT(S): Mean (SEM) carotid artery IMT measurements were 0.74 (0.01) mm among women experiencing natural menopause and 0.81 (0.02) mm among women having bilateral oophorectomy (P=.02). After adjusting for years since menopause, the mean IMT did not differ between the two groups (0.77 [0.01] mm among natural menopause and 0.76 [0.02] mm among bilateral oophorectomy groups). The age-adjusted carotid IMT was significantly positively associated with years since menopause (P=.02). CONCLUSION(S): Earlier menopause is associated with elevated subclinical atherosclerosis. Because they have on average far earlier menopause, women with bilateral oophorectomy have elevated subclinical atherosclerosis compared with women of similar age who had natural menopause.

Aged↗

Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: To determine the prevalence of insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) using baseline fasting blood measurements of glucose and insulin. DESIGN: Prospective clinical study. SETTING: Academic endocrinology unit in Palermo, Italy. PATIENT(S): Two hundred and sixty-seven women with PCOS, consecutively evaluated, and 50 consecutively selected ovulating controls. INTERVENTION(S): Fasting blood was obtained for glucose and insulin measurements from all women. For 60 women with PCOS and 20 controls an insulin tolerance test (ITT) was also performed. MAIN OUTCOME MEASURE(S): Assessment of normal and abnormal values for fasting insulin, glucose/insulin ratio, and the calculated indices of the homeostasis model assessment (HOMA), quantitative sensitivity check index (QUICKI), as well as Kitt (kinetic disappearance of glucose) values after ITT. Evaluation was performed of the ability to detect IR using these methods in obese and nonobese women with PCOS. RESULT(S): Normal insulin sensitivity was defined by insulin levels <12 mU/mL, glucose/insulin ratios of >6.4, HOMA values of <47, and QUICKI values of >0.333. In the entire PCOS groups, IR was diagnosed in 65.4% of women using glucose/insulin ratios and in 77% and 79.2% using HOMA and QUICKI. In obese women (body mass index >28 in 48% of group), IR was present in 76.7% as measured by glucose/insulin ratios but was significantly higher (95.3%) using values of either HOMA or QUICKI (P<.01). All indices correlated with Kitt values with QUICKI showing the best correlation. CONCLUSION(S): Insulin resistance was detected in approximately 80% of women with PCOS, and in 95% of obese women. The detection of IR is superior using the calculated indices HOMA and QUICKI.

Blood Glucose↗

The Women's Health Initiative could not have detected cardioprotective effects of starting hormone therapy during the menopausal transition.

The Women's Health Initiative (WHI) randomized controlled trial failed to show cardioprotection by estrogen plus progestin treatment of postmenopausal women. But by design, the WHI population was 10-fold underpowered to show cardioprotection of women starting hormone treatment during the menopausal transition. Thus, observational studies that showed cardioprotection in such women remain the only applicable clinical guide to this issue. Randomized controlled trials are urgently needed to test cardioprotection in women starting treatment during the menopausal transition.

Cardiovascular Diseases↗