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Biomedical subjects

R A Lobo

Publications and source records attributed to R A Lobo.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evidence that insulin and androgens may participate in the regulation of serum leptin levels in women.

OBJECTIVE: Although serum leptin is principally influenced by body mass, to understand the role of insulin and androgens in the regulation of serum leptin in normal weight women. DESIGN: Prospective observational study. SETTING: Academic practice in reproductive endocrinology. PATIENT(S): Twenty-one women with polycystic ovary syndrome (PCOS) of normal body weight, 8 apparently normal women with polycystic-appearing ovaries (PAO), and 21 normal women. INTERVENTION(S): Fasting blood levels of luteinizing hormone, follicle-stimulating hormone, testosterone (T), unbound T, dehydroepiandrosterone sulfate (DHEAS), insulin, insulin growth factor-binding protein-1 (IGFBP-1), and leptin. MAIN OUTCOME MEASURE(S): Comparisons of measured hormones in the different groups and correlative analysis RESULT(S): Women with PCOS had higher levels of serum luteinizing hormone, T, unbound T, DHEAS and insulin, and lower levels of IGFBP-1 compared with the normal controls, but they had similar leptin levels. Normal women with PAO had increased levels of insulin and leptin compared with controls, whereas IGFBP-1 was lower in PAO. In normal weight women with PCOS and PAO, leptin correlated positively with body weight and insulin, and negatively with IGFBP-1 and DHEAS. CONCLUSION(S): In normal weight patients serum leptin levels may be regulated in part by insulin. Androgens, on the other hand, may play a role in suppressing serum leptin.

Adult↗
PubMed1999

Alterations in low-density lipoprotein and high-density lipoprotein subclasses among Hispanic women with polycystic ovary syndrome: influence of insulin and genetic factors.

OBJECTIVE: To examine the influence of hyperandrogenism on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass levels as well as lipoprotein (a) levels in hyperandrogenic women compared with a control group. DESIGN: Case-control study. SETTING: University-based outpatient clinic. PATIENT(S): Sixteen Hispanic women with polycystic ovary syndrome were compared with 21 controls matched for age, weight, and ethnicity. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fasting serum levels of testosterone, insulin, and lipoproteins. RESULT(S): Compared with controls, women with polycystic ovary syndrome had significantly lower levels of apolipoprotein A-I (95+/-28 mg/dL versus 144+/-42 mg/dL) and HDL2a (30.9%+/-4.4% versus 36.6%+/-5.4%) but significantly higher levels of HDL3c (5.1%+/-2.2% versus 2.4%+/-1.5%). There were no statistically significant differences in LDL subclasses between groups, but there was a high incidence (54%) of the atherogenic lipoprotein phenotype B in this Hispanic population. As a group, Hispanic women with the abnormal B phenotype had significantly higher levels of insulin, HDL, HDL2b, and triglycerides. CONCLUSION(S): Hyperandrogenemia may have an adverse effect on serum lipoproteins through effects on HDL subclasses. Hispanic women may have a higher incidence of the atherogenic lipoprotein phenotype B, which may increase their risk for atherosclerosis.

Adult↗
PubMed1999

The contributions of oestrogen and growth factors to increased adrenal androgen secretion in polycystic ovary syndrome.

Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), although the expression of this enhanced secretion may be heterogeneous. Since no single factor acts in isolation, this study was performed to assess the influence of oestradiol (total and unbound), insulin, insulin-like growth factor (IGF)-I, IGF-II and the binding proteins IGFBP-I, and IGFBP-3, on basal and adrenocorticotrophic hormone (ACTH) stimulated adrenal androgen secretion in 25 women with PCOS and 10 matched ovulatory controls. Women with PCOS exhibited elevations of all androgens as well as unbound oestradiol, insulin and non-IGFBP-1 bound IGF-I. Positive correlations were noted between oestrogen and basal and ACTH stimulated delta 5 adrenal androgens. Serum IGF-I was only correlated with basal dehydroepiandrosterone sulphate (DHEA-S), while insulin exhibited a strong correlation with the delta 4 pathway and androstenedione formation in particular. This correlation was also confirmed by dividing the PCOS group into those women with and without hyperinsulinaemia. The activity of 17,20 lyase favouring androstenedione was increased in the hyperinsulinaemic women. By multivariate analyses, body mass index did not influence these findings. Although there are inherent difficulties in making major conclusions based on correlative analyses, it is suggested that oestrogen may have a greater influence on enhancing delta 5 adrenal androgen secretion, and insulin a greater effect on the delta 4 pathway. In turn, the relative importance of these influences may contribute to the heterogeneous nature of adrenal hyperandrogenism in PCOS.

Adrenal Glands↗
PubMed1999

A comparative study of transvaginal uterine ultrasound and endometrial biopsy for evaluating the endometrium of postmenopausal women taking hormone replacement therapy.

OBJECTIVE: Compare transvaginal uterine ultrasound and endometrial biopsy in evaluating the endometrium of postmenopausal women who are taking estrogen replacement therapy (ERT) or hormone replacement therapy (HRT; estrogen and progestin). DESIGN: Prospective multicenter study done in the United States with 148 healthy women with an intact uterus. A total of 121 women used hormonal preparations prescribed by personal physicians. Continuous combined HRT regimens, nonoral forms of ERT or HRT, and intrauterine devices were not allowed for 3 months before the study began. Endometrial biopsy samples were taken within 3 days of transvaginal ultrasound measurement. The uterus was scanned transversely and longitudinally. Endometrial thickness was measured at the thickest part of the longitudinal plane. RESULTS: Endometrial thickness ranged from 1.0 to 25.0 mm. The range in 126 women with a normal endometrium (determined by diagnoses of endometrial biopsies) was 1.0-25.0 mm (median, 5.0 mm); in 15 women with an abnormal endometrium, the range was 2.8-23.0 mm (median, 6.2 mm). A significant difference (p = 0.006) in endometrial thickness was seen between the 38 subjects taking ERT and HRT (median, 6.1 mm) with unexpected bleeding or spotting and the 26 untreated women in the control group (median, 4.0 mm). Overall, results were clinically inconclusive. CONCLUSIONS: Results of ultrasound as a screening technique in postmenopausal women who were taking ERT or HRT did not correlate well with results of endometrial biopsy. Unscheduled bleeding in postmenopausal women should be investigated regardless of results of ultrasonographically determined endometrial thickness. Abnormalities may be found with an endometrial thickness of less than 4 mm with or without HRT and even with no bleeding.

Adult↗
PubMed1999

Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial.

Alendronate and estrogen are effective therapies for postmenopausal osteoporosis, but their efficacy and safety as combined therapy are unknown. The objective of this study was to evaluate the addition of alendronate to ongoing hormone replacement therapy (HRT) in the treatment of postmenopausal women with osteoporosis. A total of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least 1 yr, were randomized to receive either alendronate (10 mg/day) or placebo. HRT was continued in both groups. Changes in bone mineral density (BMD) and biochemical markers of bone turnover were assessed. Compared with HRT alone, at 12 months, alendronate plus HRT produced significantly greater increases in BMD of the lumbar spine (3.6% vs. 1.0%, P < 0.001) and hip trochanter (2.7% vs. 0.5%, P < 0.001); however, the between-group difference in BMD at the femoral neck was not significant (1.7% vs. 0.8%, P = 0.072). Biochemical markers of bone turnover (serum bone-specific alkaline phosphatase and urine N-telopeptide) decreased significantly at 6 and 12 months with alendronate plus HRT, and they remained within premenopausal levels. Addition of alendronate to ongoing HRT was generally well tolerated, with no significant between-group differences in upper gastrointestinal adverse events or fractures. This study demonstrated that, in postmenopausal women with low bone density despite ongoing treatment with estrogen, alendronate added to HRT significantly increased bone mass at both spine and hip trochanter and was generally well tolerated.

Adult↗
PubMed1999

Progestogen metabolism.

There are multiple metabolic pathways for progesterone. Progestogens are metabolized differently as compared with the fate of endogenous progesterone, and the metabolites are significantly dependent upon the route of administration and the physiologic and pathologic state of the patient. Marked variations between patients have also been observed. Many organs metabolize progestogens, each in its own way. In turn, the metabolites each have different biologic potencies, which include major effects on the central nervous system. Compared with the knowledge base about progesterone metabolism, much less is known about medroxyprogesterone acetate and other C-6 and 19-NOR testosterone-derived progestogens.

Central Nervous System↗
PubMed1998

The addition of dexamethasone to antiandrogen therapy for hirsutism prolongs the duration of remission.

OBJECTIVE: To determine whether the addition of dexamethasone to antiandrogen therapy prolongs the duration of remission in women with hirsutism. DESIGN: Follow-up study of patients treated with one of four regimens: spironolactone (100 mg/d) for 1 year, dexamethasone (0.37 mg/d) for 1 year, dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 1 year, or dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 2 years. SETTING: Academic medical practice in reproductive endocrinology. PATIENT(S): Fifty-four women with hirsutism and hyperandrogenism. INTERVENTION(S): Ferriman-Gallwey-Lorenzo scores were obtained and serum levels of testosterone, unbound testosterone, and dehydroepiandrosterone sulfate were measured before therapy, every 6 months during therapy, and for 1 year after the withdrawal of therapy. MAIN OUTCOME MEASURE(S): Hirsutism scores and serum indices of hormonal changes were monitored. RESULT(S): Ferriman-Gallwey-Lorenzo scores and androgen levels remained low 1 year after the withdrawal of therapy in patients who were treated with dexamethasone, either alone or in combination with spironolactone. In patients who were treated with spironolactone alone, hirsutism scores had returned to baseline values after 1 year. CONCLUSION(S): The addition of an agent that suppresses androgen levels may be useful to prolong the duration of remission of hirsutism in women with hyperandrogenism who are treated with antiandrogens.

Adult↗
PubMed1998

Effects of different hormone replacement regimens on postmenopausal women with abnormal lipid levels. Menopause Study Group.

OBJECTIVES: A retrospective, subset analysis of the prospective Menopause Study Group data was performed to determine the effects of four conjugated estrogens (CE) + medroxyprogesterone acetate (MPA) regimens and one unopposed CE regimen on the lipid profiles of women with abnormal lipid levels (n = 525). Previously unpublished data on the entire study population were also reviewed to determine the effects of these hormone replacement regimens on blood pressure and weight (n = 1368, 1374, respectively). METHODS: During a 1-year, prospective trial, all patients took CE. Groups A and B also took continuous MPA 2.5 and 5 mg, respectively, C and D took MPA 5 and 10 mg for the last 14 cycle days of each 28-day cycle, and E took matching placebo tablets to replace MPA. RESULTS: After 1 year, all five regimens were directly associated with significant elevations in high density lipoprotein-2 (HDL2) cholesterol and significant reductions in low density lipoprotein (LDL) cholesterol (p < 0.05), although unopposed estrogen produced the greatest increase in HDL2 cholesterol. The CE + MPA regimens were also associated with significant decreases in total cholesterol. Triglyceride levels did not change significantly from baseline in any treatment group (baseline values > 1.808 mmol/l (> 160 mg/dl)), although the CE + MPA regimens were associated with a mean triglyceride decrease and CE-only women (n = 8) had a mean triglyceride increase. No regimen produced significant weight or blood pressure changes. CONCLUSIONS: This analysis suggests that hormone replacement therapy (CE + MPA), used in appropriate dosages, may alter the HDL2 cholesterol and LDL cholesterol lipoproteins in postmenopausal women with borderline lipid levels (a higher-risk population) in a cardioprotective manner.

Blood Pressure↗
PubMed1997

Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein.

OBJECTIVE: To examine the independent effects on insulin sensitivity and antioxidative activity of the three most prevalent constituents in Premarin (Wyeth-Ayerst Laboratories, Philadelphia, PA): estrone sulfate (E1S), 50%; equilin sulfate (EqS), 25%, and 17 alpha-dihydroequilin sulfate (17 alpha-ES), 15%. DESIGN: Prospective randomized cross-over study. SETTING: University of Southern California Medical Center. PATIENT(S): Eight healthy postmenopausal women, mean age 53 +/- 2 years, and mean body mass index, 26 +/- 2 kg/m2, were enrolled. INTERVENTION(S): Each woman received, in randomized succession, daily oral doses of 17 alpha-ES (0.2 mg), E1S (0.625 mg), and EqS (0.3 mg) for 30 days. MAIN OUTCOME MEASURE(S): Oxidation of low-density lipoprotein (LDL) by negatively charged LDL (LDL-) and lag phase duration and measured the plasma glucose disappearance after insulin administration (K(itt)). RESULT(S): All three estrogen preparations demonstrated antioxidant effects with E1S demonstrating the most significant changes, followed by EqS and 17 alpha-ES. Using E1S, LDL-levels decreased from a baseline of 3.91 +/- 0.9 to 2.05 +/- 0.32 mg/dL and the lag time increased from 24.5 +/- 6.0 to 87.8 +/- 11.8 minutes. Changes in insulin tolerance tests revealed improved insulin action with the various estrogens. With EqS, K(itt) increased from 3.1% +/- 0.3% to 4.3% +/- 0.3% glucose/min, was intermediate with E1S and was least with 17 alpha-ES. CONCLUSION(S): All three conjugated equine estrogens demonstrated antioxidant activity. Also, some improved insulin action was demonstrated. To our knowledge, this is the first in vivo study to examine the effects of these components which may help explain, in part, some of the cardioprotective properties ascribed to Premarin.

Adult↗
PubMed1997

Endothelin levels decrease after oral and nonoral estrogen in postmenopausal women with increased cardiovascular risk factors.

OBJECTIVE: To establish levels of plasma endothelin-1 in postmenopausal women with increased CV risk as compared with healthy premenopausal women and to measure the effects of different forms of estrogen replacement on plasma endothelin-1. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENT(S): We studied 18 postmenopausal women (mean age 53.4 +/- 4.9 years) with total cholesterol levels > 240 mg/dL divided into those with and without hypertension as well as in 10 healthy premenopausal women. INTERVENTION(S): The postmenopausal women were randomized to receive oral estrone sulfate, transdermal E2, or placebo for 30 days. MAIN OUTCOME MEASURE(S): We measured the endothelin-1 levels and total cholesterol at baseline and after 30 days of estrogen treatment. RESULT(S): In the postmenopausal women, endothelin-1 was higher (4.58 +/- 0.46 pg/mL) compared with premenopausal levels (2.80 +/- 0.46 pg/mL). In hypertensive postmenopausal women, endothelin-1 was 5.56 +/- 0.44 pg/mL. After estrogen, plasma endothelin-1 values decreased from 5.38 +/- 0.66 to 4.82 +/- 0.9 pg/mL with oral estrone sulfate, 4.84 +/- 0.25 to 4.54 +/- 0.49 pg/mL with transdermal E2, and did not change after placebo 4.76 +/- 0.71 to 4.81 +/- 0.46 pg/mL. In evaluating hypertensive women alone with estrogen therapy, plasma endothelin-1 showed the greatest decrement from 5.39 +/- 0.49 to 4.4 +/- 0.59 pg/mL (18.4%). The decrease in endothelin-1 with estrogen, which was statistically significant for the entire group, did appear to be influenced by the route of administration. Baseline plasma endothelin-1 levels were correlated positively to plasma cholesterol levels with a correlation coefficient of 0.632. CONCLUSION(S): These data provide another potential mechanism explaining the cardioprotective effects of hormone replacement therapy.

Administration, Cutaneous↗
PubMed1997

Potential enhancement of endometrial receptivity in cycles using controlled ovarian hyperstimulation with antiprogestins: a hypothesis.

OBJECTIVE: To manipulate the luteal endometrial progression by the use of antiprogestins. DESIGN: Prospective controlled clinical trial. SETTING: The IVF program of the University of Southern California School of Medicine, Los Angeles, California. PATIENT(S): Thirteen oocyte donors and 20 oocyte recipients. INTERVENTION(S): Controlled ovarian hyperstimulation of oocyte donors, administration of two doses of 2.5 mg of RU486 to the study group, and endometrial biopsies. MAIN OUTCOME MEASURE(S): Serum E2 and P levels, histologic dating of the endometrium, endometrial ultrastructure by scanning electron microscopy. RESULT(S): No difference in serum E2 or P levels was noted after RU486 administration. The histologic dating was advanced in oocyte donors as compared with recipients undergoing artificial cycles but returned to normal (in phase) after RU486. Pinopods were noted in all recipient biopsies and in donors treated with RU486 but in only one of four biopsies in donor controls. CONCLUSION(S): Cycles with controlled ovarian hyperstimulation are associated with high early luteal P levels and advanced endometrial histology. Low doses of RU486 may correct the precocious luteinization and restore endometrial receptivity.

Biopsy↗
PubMed1997

Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as high dose cyproterone acetate but results in a longer remission.

Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished to compare the effectiveness of CPA in two standard doses with GnRHa and add-back therapy and to compare the length of remission after these treatments. A total of 60 hirsute hyperandrogenic women was assigned to the following treatment groups: CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group), CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21 (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index and anagen hair shaft diameters and serum luteinizing hormone (LH) and testosterone were assessed before and every 3 months during and after treatment. All women were treated for 1 year with 1 year follow-up. At baseline hirsutism and endocrine patterns were similar in all groups. After one year of treatment, hirsutism decreased in all groups but the changes were greater (P <0.05) in the CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were similar to pretreatment values. In the GnRHa group, hirsutism increased more gradually and after 1 year of withdrawal, FGL scores and hair diameters were significantly (P <0.05) less than pretreatment values. Serum LH and testosterone increased rapidly in all three groups reaching pretreatment values by 6 months. These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back treatment appears to result in a longer remission of hirsutism in comparison with CPA.

Adult↗
PubMed1997

Cumulative conception and live birth rates after oocyte donation: implications regarding endometrial receptivity.

The purpose of the present study was to determine the cumulative likelihood of pregnancy success after repetitive cycles of oocyte donation and specifically to examine the influence of recipient age and diagnosis upon the cumulative likelihood of pregnancy in an effort to identify any potential subgroup of recipients who might have diminished endometrial receptivity. We retrospectively analysed the outcome of 418 consecutive embryo transfer cycles among 276 recipients of oocyte donation in our institution. We analysed clinical pregnancy and delivery rates in the recipients divided by age groups and diagnostic groups. For the purpose of life-table analysis, only cycles prior to and including the first cycle producing a successful pregnancy were included. Frozen-thawed embryo transfers were not included in the analysis. The overall clinical pregnancy rate was 36.2% (95% CI 31-41%) and the cumulative pregnancy rate after four cycles was 87.9%. The overall delivery rate was 29.3% (95% CI 25-33%) and the cumulative delivery rate after four cycles was 86.1%. There were no statistically significant differences in any of the rates attributable to recipient age or diagnosis. No decline in per cycle success was noted over consecutive cycles. We conclude that neither recipient age nor diagnosis plays a substantial role in the success of oocyte donation, implying that endometrial receptivity is unaltered by age or diagnosis. Furthermore, up to four successive cycles of oocyte donation are associated with the same probability of success.

Adult↗
PubMed1997

Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound.

Polycystic-appearing ovaries (PAO) on ultrasound have been described in a variety of endocrinopathies and also occur in ovulatory women. By some investigators this is merely referred to as 'PCO' (polycystic ovaries). Although there is controversy in this regard, we do not consider women with PAO/PCO who have no known endocrine disturbance to have polycystic ovary syndrome (PCOS) and therefore prefer not to use the term 'PCO' which is often equated with PCOS. We studied 15 ovulatory women with normal-appearing (NAO) ovaries on ultrasound and 15 matched ovulatory women with PAO/PCO. Compared to ovulatory women, 25 other women were studied who were considered to have PCOS. Of these, 15 were overweight and 10 were of normal weight. All the PCOS women had serum concentrations of luteinizing hormone (LH), testosterone, unbound testosterone, androstenedione and dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P < 0.01) than values in the normal women, regardless of ovarian morphology. These values were similar in the two groups of ovulatory women with NAO and PAO/PCO. Fasting insulin was elevated in women with PCOS with increased body weight (P < 0.01) and was higher than in ovulatory women with NAO and PAO/PCO and than in women of normal weight with PCOS. Serum insulin-like growth factor (IGF)-I and binding protein (BP)-3 were similar in all groups but serum IGFBP-1 was significantly (P < 0.01) lower in those women with PCOS with increased body weight, compared to all other groups. Compared to values in ovulatory women with NAO, serum IGFBP-1 was also significantly (P < 0.05) lower in women with PAO/PCO and those women with PCOS of normal weight. These lower values were similar in women with PAO/PCO and in normal weight women with PCOS. On an individual basis, an elevation of at least one serum androgen value was found in 33% of women with PAO/PCO. These data confirm that increased body weight accentuates the metabolic alterations in PCOS, but suggest that subtle endocrine disturbances, similar to those that are found in PCOS, may be uncovered in up to a third of ovulatory women with PAO/PCO. It appears that a disturbance of the IGF/IGFBP-1 axis is common and apparently closely associated with alterations in ovarian morphology.

Adult↗