Effects of royal jelly on bone metabolism in postmenopausal women: a randomized, controlled study.

OBJECTIVES: This study aimed to evaluate the effects of royal jelly (RJ) supplementation on bone metabolism in postmenopausal women. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. Seventy-two healthy postmenopausal women aged 45-60 years within 5 years after menopause were randomized into two groups: women in the RJ group (n = 36) received capsules containing dried RJ (equivalent to 3000 mg of fresh RJ); and women in the placebo group (n = 36) received placebo daily for 6 months. Bone mineral density (BMD) of the lumbar spine (L2-L4) and left proximal femur, hip structural analysis (HSA) of the left hip, and bone turnover markers were measured. RESULTS: Although women in the placebo group experienced a significant loss of BMD and deterioration in HSA parameters of the femur, no significant differences were found in these parameters in women in the RJ group. The levels of total procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase decreased significantly in the placebo group; however, the total P1NP level, a marker of bone formation, was not significantly different in the RJ group at postintervention compared with baseline. CONCLUSION: RJ consumption may ameliorate decreases in femoral BMD and strength in postmenopausal women.

Royal jelly does not prevent bone loss but improves bone strength in ovariectomized rats.

OBJECTIVE: Royal jelly (RJ) has been used for medical and nutritional purposes, and previous studies have indicated that it may have estrogenic activity. The present study investigated the effects of RJ on bone metabolism in ovariectomized (OVX) rats. METHODS: Rats (12 weeks old) were randomly divided into four groups, namely Baseline, Sham, OVX, and OVX + RJ groups. Rats in the Baseline group were killed immediately, whereas rats in the OVX and OVX + RJ groups underwent bilateral ovariectomy and those in the Sham group underwent sham operation. RJ was administered to rats in the OVX + RJ group daily for 12 weeks. At the end of the 12-week period, bone mass, bone histomorphometry, and bone mechanics were analyzed. RESULTS: Femur bone mineral density (BMD) was significantly lower in the OVX group than in the Sham group, and this decrease in BMD was not ameliorated by RJ administration. However, femur stiffness, as evaluated by a three-point bending test, was significantly higher in the OVX + RJ group than in the OVX group. CONCLUSION: The findings of the present study suggest that RJ does not prevent bone loss, but does improve bone strength in OVX rats.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly.

OBJECTIVE: Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Estrogen deficiency after menopause leads to a high risk of memory impairment and depression as well as metabolic syndrome and osteoporosis. We here investigated the effect of RJ on memory impairment and depression-like behaviors in ovariectomized (OVX) rats. METHODS: OVX rats were administered with RJ for 82 days. Hippocampus-dependent spatial memory and depression-like behaviors were assessed by the Morris water maze test and the forced swimming test, respectively. The weights of body, brain and uterus and the contents of protein and myelin galactolipids including galactosylceramide and sulfatide were measured. RESULTS: Memory impairment and depression-like behaviors in OVX rats were recovered to the levels of sham-operated rats by RJ administration. Increased body weight and decreased uterine weight in OVX rats were recovered to the levels of sham-operated rats by 17ß-estradiol (E2) administration but not by RJ administration. In contrast, brain weight was slightly increased by RJ administration but not by E2 administration. The contents of protein and myelin galactolipids were higher in the brains of RJ-administered OVX rats than in the brains of E2-administered OVX rats. CONCLUSION: The results suggest that RJ has a beneficial effect on neurological symptoms of a menopausal disorder.

Unexpected ovarian malignancy following laparoscopic excision of adnexal masses.

STUDY QUESTION: What are the frequency of, and the prognosis for, ovarian malignancies among patients who have undergone laparoscopic surgery for an adnexal mass? SUMMARY ANSWER: The rate of unexpected ovarian malignancy resected by laparoscopy was 1.5%, and the presence of an early-stage unexpected ovarian malignancy did not alter patient prognosis. WHAT IS KNOWN ALREADY: Even when laparoscopic surgery is used for the resection of an adnexal mass that is most likely benign, some patients are found to have malignant tumors post-operatively. STUDY DESIGN, SIZE, DURATION: The pathologic reports of 884 women who underwent laparoscopic resection of an adnexal mass between May 2007 and September 2013 at the Department of Obstetrics and Gynecology of Aichi Medical University Hospital, Nagakute, Japan, were reviewed retrospectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted a systematic review of the medical records of patients diagnosed post-operatively with ovarian malignancies and abstracted their demographic, clinical and pathologic data. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1128 adnexal masses were resected, and 13 patients (1.5%) had ovarian malignancies: 6 ovarian cancer (1 mucinous, 1 endometrioid G1, 1 granulosa cell and 3 carcinoid) and 7 borderline tumors (BOTs; 5 mucinous and 2 serous). Of these, two patients with mucinous BOTs underwent fertility-sparing surgery and six patients underwent staging laparotomy. Due to cyst rupture during surgery, nine patients (69.2%) were upgraded to tumor stage IC. Secondary surgeries were performed in eight patients, with a mean interval of 88.9 days (range, 39-182 days) between the surgeries. All patients were alive and without evidence of disease at follow-up (mean follow-up, 38 months; range, 6-80 months). LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study with a small case number and a short follow-up period. WIDER IMPLICATIONS OF THE FINDINGS: The presence of an early-stage unexpected ovarian malignancy did not alter the patient's prognosis, even if there was a significant delay in surgical staging after the finding of an unexpected malignancy during laparoscopy. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study and the authors report no conflicts of interest.

Effect of the ethanol extract of Pleurotus eryngii on bone metabolism in ovariectomized rats.

OBJECTIVE: Postmenopausal bone loss and the possible progression to osteoporosis are a major health concern. Mushrooms have been recognized as functional foods. Pleurotus eryngii extract has been reported to have estrogenic activity, suggesting that its consumption may mitigate postmenopausal bone loss. The aim of the present study was to determine the effect of supplementation with an ethanol extract of P. eryngii on bone metabolism in a postmenopausal osteoporosis rat model. METHODS: Female 12-week-old Wistar rats were subjected to either sham operation or bilateral ovariectomy. The ovariectomized rats were then subdivided into two groups: one fed the extract and the other not. Twelve weeks after surgery, indices of bone mass, bone histomorphometry, and bone mechanics were measured. RESULTS: The right femur bone mineral content and density of the ovariectomized group were significantly lower than in the Sham group, and extract supplementation did not have any significant effect on these differences. Furthermore, ovariectomy significantly increased measures of mineralizing surface and bone formation rates; again, extract supplementation again had no significant effect. CONCLUSION: Our findings suggest that the ethanol extract of P. eryngii does not alter bone metabolism in ovariectomized rats, suggesting that consumption of P. eryngii may not be beneficial in slowing bone loss after menopause.

Effect of medroxyprogesterone acetate on endothelium-dependent vasodilation in postmenopausal women receiving estrogen.

BACKGROUND: Estrogen increases endothelium-dependent vasodilation in postmenopausal women. However, use of progestins in combination with estrogen may counter beneficial effects of estrogen on endothelium. We investigated the effect of medroxyprogesterone acetate (MPA) on estrogen-induced increase in endothelium-dependent vasodilation in postmenopausal women. METHODS AND RESULTS: Postmenopausal women were treated daily with conjugated equine estrogen (CEE) 0.625 mg (n=14), CEE 0.625 mg and MPA 2.5 mg (n=15) or CEE 0.625 mg and MPA 5.0 mg (n=16) for 3 months. Plasma lipids and hormones were measured before and after treatment. Vasodilatory responses of the brachial artery were evaluated by measuring flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation by use of high-resolution ultrasonography. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO(4) while kinetics of conjugated diene formation was monitored. Plasma total and LDL cholesterol concentrations were decreased significantly in all groups. CEE increased FMD significantly, from 4.5+/-1.7% to 8.5+/-2.8% (P<0.001). Addition of MPA reversed this effect in a concentration-dependent manner (for MPA 2.5 mg, from 5.0+/-3.2% to 6.2+/-3.1%; for MPA 5.0 mg, from 4.9+/-3.4% to 3.6+/-3.7%; P=NS for each). No treatment significantly altered nitroglycerin-induced dilation. Lag time for conjugated diene formation was prolonged significantly in all groups, and the oxidation rate was significantly reduced. CONCLUSIONS: Concurrent MPA administration may offset favorable effects of estrogen on endothelial function in postmenopausal women. Because MPA did not diminish LDL-lowering and antioxidant effects of estrogen, MPA-induced inhibition of endothelium-dependent vasodilation may be independent of changes in oxidative susceptibility and plasma concentration of LDL.

Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women.

OBJECTIVES: The purpose of this study was to investigate the susceptibility of estrogen-induced small low density lipoprotein (LDL) particles to oxidation. BACKGROUND: Estrogen replacement therapy in postmenopausal women has an antioxidant effect that opposes oxidation of LDL particles. Estrogen-induced increases in plasma triglyceride concentrations, however, decrease LDL particle size, which may act counter to this antioxdant effect. It has not been evaluated whether estrogen-induced small LDL particles are atherogenic. METHODS: In 24 lean and healthy postmenopausal women treated with conjugated equine estrogen (0.625 mg daily) for three months, plasma lipid concentrations and diameter of LDL particles were measured before and after therapy. Susceptibility of LDL to oxidation was determined by measuring the concentration of thiobarbituric acid-reactive substances (TBARS) after incubation with CuSO4. RESULTS: Estrogen significantly decreased plasma concentrations of total cholesterol, LDL-cholesterol and apolipoprotein B, while increasing concentrations of triglyceride, high-density lipoprotein cholesterol and apolipoprotein A-I. Estrogen-induced changes in LDL particle diameter correlated negatively with changes in plasma triglyceride concentrations (r = -0.55, p < 0.005) and with changes in concentrations of LDL-derived TBARS (r = -0.49, p < 0.005). In subjects with substantial estrogen-induced plasma triglyceride increases, estrogen significantly reduced the diameter of LDL particles (p < 0.05) and significantly increased the concentration of LDL-derived TBARS (p < 0.05). In contrast, estrogen significantly reduced the concentration of LDL-derived TBARS (p < 0.05) and caused no significant change in LDL particle diameter in subjects whose plasma triglyceride concentration was unchanged with estrogen therapy. CONCLUSIONS: Because estrogen-induced plasma triglyceride increases may produce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a triglyceride increase.

Effects of combination therapy with estrogen plus simvastatin on lipoprotein metabolism in postmenopausal women with type IIa hypercholesterolemia.

We investigated the effects of estrogen and simvastatin, administered both alone and in combination, on the plasma lipid levels and lipoprotein-related enzymes in 45 postmenopausal women with type IIa hypercholesterolemia. They received 0.625 mg conjugated equine estrogen (n=15), 5 mg simvastatin (n=15), or the combination (n=15) daily for 3 months. We measured the concentrations of cholesterol and triglyceride in the plasma, and in the very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL)1 (1.019

Lipoprotein metabolism in postmenopausal and oophorectomized women.

OBJECTIVE: To investigate the mechanisms of accumulating cholesterol, and to analyze the metabolism of excess tissue cholesterol in women with low plasma levels of sex steroid hormones. METHODS: We measured plasma concentrations of cholesterol, triglyceride, apolipoproteins, sex steroid hormones, and lecithin cholesterol acyltransferase activity in 20 premenopausal, ten postmenopausal, and ten bilaterally oophorectomized women. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in postheparin plasma. We compared the three groups and evaluated a correlation between lipid metabolism and sex steroid hormone concentrations. RESULTS: The mean plasma low-density lipoprotein (LDL) cholesterol level, lecithin cholesterol acyltransferase activity, and postheparin plasma lipoprotein lipase activity were higher in the postmenopausal and surgically menopausal groups. The mean plasma high-density lipoprotein (HDL) cholesterol concentration and postheparin plasma hepatic triglyceride lipase activity did not differ significantly among the three groups. The plasma LDL cholesterol level and postheparin plasma lipoprotein lipase activity showed a significantly negative correlation with plasma concentration of estrone (LDL: r = 0.64, P < .001; lipoprotein lipase: r = 0.54, P < .005) and estradiol (LDL: r = 0.65, P < .001; lipoprotein lipase: r = 0.47, P < .01), but not with that of testosterone. There was no significant relationship between postheparin plasma hepatic triglyceride lipase activity and plasma sex steroid hormones. Plasma lecithin cholesterol acyltransferase activity correlated significantly with plasma LDL cholesterol concentration, but not with levels of sex steroid hormones. CONCLUSION: Because of low endogenous estrogens, enhanced postheparin plasma lipoprotein lipase activity may lead to an elevated plasma LDL cholesterol concentration in postmenopausal and bilaterally oophorectomized women. We demonstrated an accelerated cholesterol esterification in HDL cholesterol that may have been induced by LDL cholesterol accumulation, although the HDL cholesterol concentration remained unchanged.

Effect of estrogen on the size of low-density lipoprotein particles in postmenopausal women.

OBJECTIVE: To investigate the effects of estrogen on the size o low-density lipoprotein (LDL) particles in postmenopausal women. METHODS: We treated 20 postmenopausal women with 0.625 mg of conjugated equine estrogen daily for 3 months and measured the plasma levels of total cholesterol, triglyceride, high-density lipoprotein (HDL), and apolipoproteins A-I, A-II, and B before and after therapy. We also analyzed concentrations of LDL cholesterol and LDL apolipoprotein B. The diameter of LDL particles was determined by gradient gel electrophoresis. RESULTS: Estrogen caused significant decreases in the plasma levels of total cholesterol and apolipoprotein B and significant increases in the plasma levels of triglyceride, HDL cholesterol, and apolipoprotein A-I and A-II. Mean levels of LDL cholesterol and LDL apolipoprotein B were reduced significantly (by 16.31%, P < .001, and 16.91%, P < .001, respectively) after estrogen treatment. Estrogen also significantly reduced the size of LDL particles, from 25.74 +/- 0.66 (mean +/- standard deviation) to 24.95 +/- 0.78 nm (P < .001). The LDL particle diameter correlated negatively with the plasma level of triglyceride (pre-treatment: r = 0.87, P < .001; post-treatment: r = 0.88, P < .001). Estrogen significantly increased the prevalence of LDL subclass pattern B, from 30 to 65% (P < .03). CONCLUSION: Estrogen affects lipid metabolism favorably by reducing the plasma concentration of LDL particles. Estrogen-induced increase in the plasma level of triglyceride appears to reduce the size of LDL particles.

Estrogen-induced small low-density lipoprotein particles in postmenopausal women.

OBJECTIVE: To investigate the mechanisms of an estrogen-induced decrease in the size of low-density lipoprotein (LDL) particles in postmenopausal women. METHODS: Twenty postmenopausal women were treated with conjugated equine estrogen, 0.625 mg daily, for 3 months. Plasma levels of total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and apolipoproteins AI, AII, and B were measured before and after therapy. We analyzed total, free, and esterified cholesterol, triglyceride, phospholipid, and apolipoprotein B levels in the LDL. Cholesterol, triglyceride, and phospholipid concentrations were measured by enzymatic methods. Apolipoprotein AI, AII, and B levels were determined by immunoturbidimetric assay. The diameter of LDL particles was determined by gradient gel electrophoresis. RESULTS: Estrogen reduced significantly the plasma levels of total cholesterol and apolipoprotein B and increased significantly the plasma levels of triglyceride, HDL cholesterol, and apolipoproteins AI and AII. The ratio of cholesteryl ester to apolipoprotein B was significantly reduced, whereas the ratio of triglyceride to apolipoprotein B was significantly increased after such treatment. The plasma level of triglyceride showed a positive correlation with the ratio of LDL-triglyceride/apolipoprotein B (r = .40, P < .01), and a negative correlation with the ratio of LDL-cholesteryl ester/apolipoprotein B (r = -.55, P < .001). Estrogen treatment reduced significantly the diameter of LDL particles (25.79+/-1.13 nm versus 24.94+/-1.02 nm, P < .001). The diameter of the LDL particle was correlated negatively with the plasma level of triglyceride (r = -.84, P < .001) and the ratio of LDL-triglyceride/apolipoprotein B (r = -.58, P < .001), and positively with the ratio of LDL-cholesteryl ester/apolipoprotein B (r = .57, P < .001). CONCLUSION: The results of this study indicate that an increase in the triglyceride plasma level induced by estrogen therapy appeared to produce small triglyceride-rich and cholesteryl ester-poor LDL particles that were of small size.

Small low-density lipoprotein particles in women with natural or surgically induced menopause.

OBJECTIVE: To investigate the mechanism of the decrease in the size of low-density lipoprotein (LDL) particles in women with natural menopause and women with surgically induced menopause. METHODS: We measured plasma levels of total cholesterol; triglycerides; high-density lipoprotein (HDL) cholesterol; apolipoproteins A-I, A-II, and B; and sex hormones in 45 women; 15 women were premenopausal, 15 were naturally postmenopausal, and 15 were surgically menopausal. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in postheparin plasma. Concentrations of total cholesterol and of apolipoprotein B in LDL also were measured. Low-density lipoprotein particle diameter was determined by gradient gel electrophoresis. RESULTS: Plasma levels of total cholesterol, triglycerides, apolipoprotein B, LDL-total cholesterol, LDL-apolipoprotein B, and the activity of postheparin plasma lipoprotein lipase were significantly higher and concentrations of estrone and estradiol were significantly lower in the naturally postmenopausal and surgically menopausal women than in the premenopausal women. Plasma levels of HDL cholesterol and apolipoproteins A-I and A-II and postheparin plasma hepatic triglyceride activity did not differ significantly between groups. The diameter of LDL particles was significantly reduced in the naturally (25.29 +/- 0.19 nm) and surgically (25.29 +/- 0.22 nm) menopausal women compared with the premenopausal women (25.88 +/- 0.22 nm). Plasma triglyceride levels were negatively correlated with LDL particle diameter in all three groups (premenopausal group: r = -0.64, P < .01; naturally postmenopausal group: r = -0.62, P < .01; and surgically menopausal group: r = -0.76, P < .001). The prevalence of LDL subclass pattern B was significantly increased in the naturally (67%, P < .05) and surgically (60%, P < .05) menopausal women. CONCLUSION: The plasma concentration of LDL particles was increased after menopause, whether natural or surgically induced. An increase in plasma triglyceride levels in women with low levels of endogenous estrogen appeared to cause the size of LDL particles to be reduced.

Lipid transfer reactions and lipid composition of low-density lipoprotein particles in postmenopausal women receiving estrogen.

OBJECTIVE: To investigate the effects of estrogen on lipid transfer reactions and lipid composition of low-density lipoprotein (LDL) particles in postmenopausal women. METHODS: Twelve postmenopausal women were treated with conjugated equine estrogen, 0.625 mg daily, for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also determined the amount of total, free, and esterified cholesterol, triglyceride, and apolipoprotein B in LDL. To evaluate lipid transfer reactions, plasma samples were incubated at 37C for 24 hours, and replacement of cholesteryl ester by triglyceride in LDL particles was analyzed. Cholesterol and triglyceride concentrations were measured enzymatically. Apolipoprotein B concentrations were determined by an immunoturbidimetric assay. RESULTS: Estrogen significantly reduced the plasma levels of total cholesterol and significantly increased those of triglyceride and HDL cholesterol. The ratio of cholesteryl ester to apolipoprotein B was reduced significantly, whereas the ratio of triglyceride to apolipoprotein B increased significantly after estrogen treatment. Both before and after estrogen treatment, incubation of plasma induced a significant increase in the ratio of LDL-triglyceride to apolipoprotein B with a concomitant decrease in the ratio of LDL-cholesteryl ester to apolipoprotein B. Incubation-induced changes in these ratios were significantly enhanced by estrogen therapy. The plasma concentration of triglyceride was correlated positively with incubation-induced changes in the ratio of LDL-triglyceride to apolipoprotein B (r = .83, P < .001) and correlated negatively with changes in the ratio of LDL-cholesteryl ester to apolipoprotein B (r = -.61, P < .01). CONCLUSION: Estrogen-induced increase in the plasma level of triglyceride may enhance lipid transfer reactions, resulting in triglyceride-rich and cholesteryl ester-poor LDL particles.

Lipoprotein particles in preeclampsia: susceptibility to oxidative modification.

OBJECTIVE: To investigate the susceptibility to oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in women with preeclampsia. METHODS: Plasma levels of total cholesterol, total triglyceride, and concentrations of cholesterol, triglyceride, and protein in LDL and HDL were measured in 12 preeclamptic women and 12 normal pregnant women. Oxidation of LDL or HDL was assessed by incubation with copper ions and evaluated by monitoring the kinetics of conjugated diene formation. RESULTS: The plasma levels of total triglyceride and concentration of LDL protein were significantly higher in preeclamptic women than in normals. Levels of HDL lipid did not differ significantly. Analysis of kinetics of conjugated diene production showed a significantly shorter lag time for LDL (83.1 +/- 5.5 minutes versus 67.4 +/- 10.2 minutes, P <.001) and HDL (76.9 +/- 7.3 minutes versus 59.5 +/- 9.2 minutes, P <.001) and a significantly higher oxidation rate for LDL (3.6 +/- 0.4 nmol/minutes/mg LDL versus 4.4 +/- 1.0 nmol/minutes/mg LDL, P <.05) in preeclamptic women. CONCLUSION: Low-density lipoprotein and HDL particles were more susceptible to oxidative modification, and plasma concentration of LDL particles, but not of HDL particles, was increased in preeclampsia.

Effect of estrogen and simvastatin on low-density lipoprotein subclasses in hypercholesterolemic postmenopausal women.

OBJECTIVE: To identify the effects of estrogen and simvastatin, individually and in combination, on the levels of low-density lipoprotein (LDL) subclasses in postmenopausal women with type IIa hypercholesterolemia. METHODS: Fifty-five postmenopausal women with type IIa hypercholesterolemia were assigned randomly to 0.625 mg of conjugated equine estrogen (n = 20), 5 mg of simvastatin (n = 18), or both (n = 17) daily for 3 months. Cholesterol, triglyceride, and apolipoprotein B levels in the plasma and in the LDL1 (density 1.019-1.045 g/mL) and LDL2 (density 1.045-1.063 g/mL) fractions were measured before and after treatment. RESULTS: Estrogen treatment significantly reduced LDL1 cholesterol and LDL1 apolipoprotein B levels by 18.4% and 20.8%, respectively; simvastatin treatment by 21.9% and 29.2%, respectively; and combination therapy by 38.5% and 34.4%, respectively. In contrast to estrogen or simvastatin treatment, the combination therapy also significantly lowered the levels of LDL2 cholesterol by 19.5% and LDL2 apolipoprotein B by 30.5%. Posttreatment levels of total cholesterol, LDL1 cholesterol, and LDL1 apolipoprotein B were significantly lower after combination treatment than after estrogen treatment. Estrogen treatment, but not combination therapy, significantly increased total plasma triglyceride levels (103.1+/-26.0 mg/dL to 138.8+/-75.6 mg/dL, P < .01). Significantly more patients receiving combination therapy than those receiving estrogen had total and LDL cholesterol concentrations reduced to target levels. CONCLUSION: Combination therapy with estrogen and simvastatin favorably affected lipid metabolism by reducing large and small LDL particles and prevented the estrogen-induced increase in plasma triglyceride levels.

Lipolytic enzyme effect on small low-density lipoprotein particles in women treated with estrogen.

OBJECTIVE: To test whether hydrolysis of low-density lipoprotein (LDL) triglyceride by lipolytic enzymes decreases the size of LDL particles in women treated with estrogen replacement. METHODS: Fifteen postmenopausal women received 0.625 mg conjugated equine estrogens daily for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also assayed levels of total, free, and esterified cholesterol, triglyceride, and protein in LDL. Plasma samples were incubated at 37C for 24 hours and LDL fractions were isolated by ultracentrifugation. After LDL samples were further incubated with or without lipoprotein lipase (500, 700, and 1000 ng/mL) at 37C for 24 hours, LDL triglyceride, LDL protein, and the diameter of LDL particles were measured. RESULTS: Estrogen decreased total cholesterol and increased triglyceride and HDL cholesterol in plasma. Estrogen treatment decreased the ratio of cholesteryl ester/protein, whereas the ratio of triglyceride/protein increased. Estrogen decreased LDL particle diameter. Incubation of plasma increased the ratio of LDL triglyceride/protein from 0.40 +/- 0.14 to 0.48 +/- 0.15 (P <.05) and decreased the ratio of LDL cholesteryl ester/protein from 1.17 +/- 0.25 to 1.09 +/- 0.22 (P <.05), but LDL particle diameter did not change. Incubation of LDL with lipoprotein lipase reduced the LDL triglyceride/protein ratio, and decreased the diameter of LDL particles from 25.61 +/- 0.87 nm to 24.89 +/- 0.88 nm (500 ng/mL, P <.05), 24.62 +/- 1.20 nm (700 ng/mL, P <.05), and 24.67 +/- 1.19 nm (1000 ng/mL, P <.05). CONCLUSION: In women treated with estrogen, hydrolysis of triglyceride in LDL particles might be accompanied by reduced particle size.

Effect of prenatal melatonin exposure on gonadotropins and prolactin secretion in male and female rat pups.

We evaluated whether melatonin administration to pregnant rats during the final week of pregnancy affects prepubertal secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin in offspring. Melatonin was administered in the drinking water from day 14 to delivery. LH, FSH and prolactin concentrations were determined in plasma sampled from offspring between 5 and 30 days in the dark portion of the diurnal cycle. Administration of 2 or 20 microg/ml melatonin did not affect LH or FSH in male or female offspring. The 20-microg/ml dose caused a significant increase in prolactin in males and females at day 15. In contrast, melatonin, 2 or 20 microg/ml, decreased prolactin at days 25 and 30 in females and day 25 in males. Thus, prenatal melatonin exposure alters prolactin secretion, but not that of LH and FSH in infantile and prepubertal male and female rats.