Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire

OBJECTIVE: In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire. DESIGN: Double-blind randomized trial. SETTING: Healthy volunteers in a multicenter research environment. PATIENT(S): Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire. INTERVENTION(S): 4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107). MAIN OUTCOME MEASURES: Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire. RESULT(S): Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated. CONCLUSION(S): Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.     

Molecular cloning of a beta-glucan pattern-recognition lipoprotein from the white shrimp Penaeus (Litopenaeus) vannamei: correlations between the deduced amino acid sequence and the native protein structure

The hemolymph pattern-recognition beta-glucan binding protein from the white shrimp Penaeus (Litopenaeus) vannamei is also a high density lipoprotein (betaGBP-HDL) involved in innate immunity. The betaGBP-HDL full length cDNA sequence determined was 6.3 kb long, and contains a long 3'UTR region with a polyadenylation signal and a poly-A+ tail. The open reading frame is 1454 amino acids long and the N-terminal residue of the mature protein is localized in position 198 of the ORF. Comparison of the betaGBP-HDL amino acid sequence against GenBank detected only significant similarity to betaGBP from the crayfish Pacifastacus leniusculus. betaGBP-HDL is expressed in hepatopancreas, muscle, pleopods and gills, but not in hemocytes as determined by RT-PCR. We discuss the analysis of the deduced primary sequence in terms of the predicted secondary structure, glucanase-like and RGD motives relevant to its dual roles in defence and lipid transport.     

Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies

To assess whether risk of breast cancer in young women is associated with differences in luteal-phase hormone production and to attempt to explain differences in risk of breast cancer of young Shanghai Chinese and Los Angeles white women, two concurrent case-control studies of serum hormone concentrations were conducted. Both studies were carefully controlled for the possible confounding effects of age, weight, height, pregnancy history, and day of the menstrual cycle, by individually matching cases and controls on these factors. Case eligibility was limited to women with localized breast cancer. Sixteen of 39 Shanghai breast-cancer cases were sampled prior to the histologic diagnosis of their disease. The remaining 23 Shanghai cases and all 42 Los Angeles cases were diagnosed, and treated by surgery only, at least six months prior to hormonal evaluation. All subjects were sampled on day 22 of the menstrual cycle. Overall, cases had 13.5% higher serum estradiol concentrations (p=0.038) with a case-to-control excess of 16.6% in Shanghai subjects (p=0.089) and 10.8% in Los Angeles subjects (p=0.23). There were no appreciable differences in amounts of sex-hormone binding globulin between cases and controls. Cases had lower progesterone levels than controls, but the situation was reversed when the analysis was restricted to subjects with evidence of ovulation. Los Angeles controls had 20.6% greater estradiol concentrations than Shanghai controls (p=0.036); adjustment for body weight accounted for only 25.7% of this difference. This higher level of estradiol in Los Angeles women could be an important part of the explanation of the two-to-three-fold differences in breast cancer incidence rates of women under age 45 in Shanghai and Los Angeles.Drs Bernstein, Ross, Pike and Henderson and Ms Hanisch are in the Department of Preventive Medicine, University of Southern California School of Medicine, 1420 San Pablo Street, PMB A-202, Los Angeles, CA 90033. Drs Yuan and Gao are with the Shanghai Cancer Institute, 2200 Xie Tu Road, Shanghai, People's Republic of China. Drs Lobo and Stanczyk are in the Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Women's Hospital, 1240 North Mission Road, Los Angeles, CA 90033. Reprint requests should be addressed to Dr Bernstein. This work was supported by grants CA17054 and CA33512 from the National Institutes of Health.     

Polycystic ovary syndrome after menopause: a case report

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by characteristic ovarian morphology on ultrasound, hyperandrogenism and chronic anovulation. Little is known about zhat happens to ovarian morphology or testosterone production in women with PCOS after menopause, and it is unclear how these women should be treated for the complaint of hirsutism. CASE: A 65-year-old woman presented with elevated testosterone levels, hirsutism and insulin resistance. Laparoscopic bilateral salpingo-oophorectomy (BSO) was performed, and following the procedure the testosterone levels normalized, although the ovaries were normal histologically. CONCLUSION: Laparoscopic BSO is a relatively safe, definitive treatment for postmenoapusal women with PCOS.     

Does elevated body mass modify the influence of postmenopausal estrogen replacement on atherosclerosis progression: results from the estrogen in the prevention of atherosclerosis trial

OBJECTIVE: To determine whether the estrogen-related reduction in atherosclerosis progression demonstrated in the estrogen in the prevention of atherosclerosis trial (EPAT) is modified by body mass index (BMI). STUDY DESIGN: Subgroup analyses were performed using data from EPAT, a randomized, double-blind, placebo-controlled trial designed to determine whether unopposed 17beta-estradiol administered for a 2-year treatment period reduces the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary trial endpoint was the rate of change of common carotid artery intima-media thickness (IMT). In this subgroup analysis, the sample was divided into 122 women with BMI<30 kg/m(2) and 77 women with BMI> or =30 kg/m(2). Statistical analysis was performed using mixed general linear models to evaluate whether the treatment effects on IMT progression rates differed in the two BMI groups. RESULTS: There was no significant difference in the estradiol treatment effect on IMT progression rates between postmenopausal women with BMI<30 vs. > or =30 kg/m(2) (P=0.52). In the 77 subjects who did not use lipid-lowering therapy, there was significant improvement in IMT with estradiol treatment that was evident in both BMI groups (P=0.48 for differences between BMI groups). CONCLUSIONS: In contrast to the epidemiological observation that obese postmenopausal women do not derive benefit from estrogen replacement therapy, results of this study indicate that estradiol treatment is beneficial in preventing progression of atherosclerosis regardless of initial BMI. CONDENSATION: Estradiol treatment is beneficial in preventing progression of atherosclerosis in postmenopausal women not receiving lipid-lowering therapy, regardless of their initial body mass index.     

Effects of leucine supplementation on the body composition and protein status of rats submitted to food restriction

OBJECTIVE: Acute administration of leucine has been shown to stimulate certain protein synthesis related anabolic processes. However, the effect of chronic leucine administration in a catabolic situation caused by food restriction (FR) has not been established. We therefore evaluated the effect of chronic leucine supplementation on the body composition and some indicators of protein nutritional status of rats submitted to FR. METHODS: Adult male Wistar rats were submitted to 50% FR for 6 weeks. The control group received the AIN-93M diet and the leucine group received the same diet supplemented with 5.91 g L-leucine/kg ration. We then determined carcass chemical composition, serum leptin, albumin and total protein concentrations, and protein, DNA and RNA concentrations in gastrocnemius muscle and liver. RESULTS: No difference in final body weight was observed between groups. However, the leucine group presented a lower amount of body fat (P < 0.05). Leptin concentration showed a directly proportional correlation with the amount of body fat (r = 0.88, P < 0.05), but no significant difference in serum leptin concentration was observed between groups (P = 0.08). Regarding protein nutritional status, liver protein concentration was higher in the leucine group (P < 0.05). In the gastrocnemius muscle, a higher RNA concentration (P < 0.05) and a tendency towards higher DNA concentration (P = 0.06) were observed in the leucine group. CONCLUSION: The results indicate that low-dose leucine supplementation increases body fat loss and improves liver protein status and the capacity of muscle protein synthesis in rats submitted to FR.     

Options in advanced non-small cell lung cancer: a review and report on a phase II study of vinorelbine plus gemcitabine

Although platinum-containing regimens prolong survival in advanced non-small cell lung cancer (NSCLC), toxicity remains substantial. There is a clear need for a nonplatinum-based regimen which is active, well tolerated, and suitable for outpatient administration. Vinorelbine and gemcitabine have different mechanisms of action and are both active in NSCLC. A phase II trial was undertaken to evaluate activity and tolerability when the two drugs were administered as a first-line combination regimen in 32 patients with stage IIIB/IV disease. Gemcitabine was administered at a dose of 1,000-1,250 mg/m2 together with vinorelbine 25 mg/m2 on days 1 and 8 of a 21-day cycle. The overall response rate was 25%, median survival 8.3 months and one-year survival rate 38% (48% in patients of performance status 0-1). Grade 3/4 neutropenia was observed in 38% of 148 treatment cycles, however, thrombocytopenia was infrequent and there was no grade 3/4 anemia. Nonhematological toxicity was minimal. The response and survival rates experienced were comparable with standard platinum-based combinations. Ongoing randomized trials will further define the role of the vinorelbine/gemcitabine combination in advanced NSCLC.