Effects of low dose oral contraceptives on very low density and low density lipoprotein metabolism.

Oral contraceptives (OC) raise plasma triglyceride and VLDL levels, which may be of concern, since some conditions characterized by elevated triglycerides are associated with atherosclerosis. To identify the responsible mechanism, we studied 11 healthy premenopausal women, 5 of whom were taking OC containing 0.035 mg ethinyl estradiol, and 6 of whom were not. Their rates of VLDL and LDL metabolism were measured by endogenously labeling apoB, the protein component of VLDL and LDL, by an intravenous infusion of deuterated leucine. OC use had the greatest effect on the large, triglyceride-rich VLDL subfraction (Sf 60-400), increasing plasma levels threefold and production rates fivefold (P < 0.05). Among OC users, small VLDL (Sf 20-60) levels were 2.2 times higher, and production rates were 3.4-fold higher (P < 0.05). The fractional catabolic rates of large and small VLDL were similar among OC users and nonusers. LDL levels and metabolic rates were not significantly different between the two groups. Thus, contemporary low dose OC substantially raise VLDL levels by increasing the production rate of large, triglyceride-rich VLDL, and not by slowing VLDL catabolism. Since VLDL catabolism is not impaired, we speculate that the hypertriglyceridemia induced by OC may be less atherogenic than that of hypertriglyceridemia resulting from impaired lipolysis. This may explain why long-term OC use does not appear to promote atherosclerosis.

PIP: At Brigham and Women's Hospital in Boston, Massachusetts, data on 5 women aged 22-24 years using low-dose oral contraceptives (OCs) containing .035 mg ethinyl estradiol were compared with data on 6 women aged 23-27 years not using OCs so researchers could study the metabolism of individual very low density lipoprotein (VLDL) subfractions of low density lipoprotein (LDL) in users of low-dose OCs and nonusers. Specifically, they wanted to determine the mechanisms by which OC use increases plasma VLDL and triglyceride levels. They infused a nonradioactive amino acid tracer (D3-leucine) intravenously into the 11 women to endogenously label the primary protein component of VLDL and of LDL, apoB, allowing them to measure VLDL and LDL synthesis and catabolism. OC users had large triglyceride-rich VLDL subfraction plasma levels 3 times higher than those of nonusers (20.2 nmol/l vs. 6.7 nmol/l; p , .05). OC use increased large, triglyceride-rich VLDL subfraction production rates 5-fold (16.7 nmol/kg/d vs. 3.4 nmol/kg/d; p .005). OC users had 2.2 times higher small VLDL subfraction levels (36.7 nmol/l vs. 16.7 nmol/l; p .05) and 3.4 times higher small VLDL subfraction production rates (22.5 nmol/kg/d vs. 6.7 nmol/kg/d; p .01) than nonusers. The fractional catabolic rates of large and small VLDL were essentially the same for OC users and nonusers (19.4 pool/d vs. 18.2 pool/d and 15.1 pool/d vs. 17 pool/d). Thus, low-dose OC use increases VLDL levels via a rise in the production rate of large VLDL and not by impeding VLDL catabolism. Learning that low-dose OCs do not curb VLDL catabolism, the researchers proposed that the OC-induced hypertriglyceridemia is less likely to be atherogenic than impaired lipolysis induced hypertriglyceridemia. This hypothesis may provide the answer as to why longterm OC use does not apparently foster atherosclerosis.

Differential metabolism of human VLDL according to content of ApoE and ApoC-III.

We studied the metabolism of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) particles that did or did not have apolipoprotein E (apoE) in 12 normolipidemic women by endogenously labeling plasma apolipoprotein B. The plasma was separated into bound (E+) and unbound (E-) fractions by use of a monoclonal antibody (1D7), and the fractions were ultracentrifuged to yield E+ and E- subfractions of light and dense VLDL and IDL. VLDL E+ and IDL E+ were produced mainly by the liver. VLDL E+ and IDL E+ had lower fractional catabolic rates and much higher apolipoprotein C-III (apoC-III) content than did the corresponding E- particles. Most light VLDL apoE+ underwent lipolysis to dense VLDL E+ with reduced apoC-III content, which was removed from the circulation without conversion to IDL. In contrast, most light VLDL apoE-, poor in apoC-III, was removed from the circulation, and a smaller proportion underwent lipolysis to dense VLDL E-. Most dense VLDL E- underwent lipolysis to IDL E-. The rate constant for lipolysis of dense VLDL to IDL was greater for E- than for E+, and the rate constant for clearance from plasma was greater for dense VLDL E+ than for E-. In conclusion, metabolism of human VLDL particles is influenced by their content of apoE, further modulated by the coexistence of apoC-III.

Effect of postmenopausal estrogen replacement on plasma Lp(a) lipoprotein concentrations.

BACKGROUND: Women who receive postmenopausal estrogen replacement experience a lower rate of coronary heart disease than women who do not receive these hormones. Evidence suggests that mechanisms in addition to decreases in plasma low-density lipoprotein levels and increases in high-density lipoprotein concentrations are responsible for the apparent beneficial effect of estrogens. Therefore, we studied the effect of estrogen on plasma Lp(a) lipoprotein, newly suggested to be a risk factor for coronary heart disease in postmenopausal women. METHODS: The 31 healthy, normolipidemic subjects received placebo and conjugated equine estrogens (0.625 and 1.25 mg/d) for 3-month periods in a randomized, double-blind, crossover trial. RESULTS: The mean Lp(a) lipoprotein concentration was 20.4 +/- 14.6 mg/dL during placebo treatment; it decreased by 14% (P < .01) with 0.625 mg of conjugated estrogens and by 16% (P < .005) with 1.25 mg. The Lp(a) lipoprotein concentration during placebo treatment was not significantly correlated with the responses to either dose of estrogen. There was no effect of estrogen on the plasma concentration of cholesterol ester transfer protein, suggesting that this protein is not involved in estrogen-induced changes in very-low-density lipoprotein or high-density lipoprotein concentrations and composition. CONCLUSIONS: Estrogen decreases the plasma Lp(a) lipoprotein concentration, which could explain some of the protective effect of estrogen replacement therapy on coronary heart disease.

Effect of estrogen on very low density lipoprotein and low density lipoprotein subclass metabolism in postmenopausal women.

Estrogen decreases low density lipoprotein (LDL) particle size, and smaller LDL particles are associated with coronary atherosclerosis. To understand the metabolic basis for this change, we studied the effect of oral 17 beta-estradiol (2 mg/day) on apolipoprotein B-100 (apoB) metabolism, in eight healthy postmenopausal women. The study was a randomized, double blinded, placebo-controlled, cross-over trial with intervention sequences of 6 weeks each. ApoB in very low density lipoprotein, intermediate density lipoprotein, and LDL subclasses was endogenously labeled with [D3]L-leucine, and metabolic rates were calculated by computer modeling. The overall effect of oral estrogen therapy on apoB metabolism was to accelerate the fractional catabolic rates of all particles studied and production rates of all except IDL. For light LDL (density = 1.019-1.036 g/mL), estrogen increased the mean fractional catabolic rate by 63% from 0.59 to 0.96 pools/day (P = 0.02), whereas the production rate increased by a lesser amount (42%) from 575 to 817 mg/day (P = 0.10). These metabolic changes reduced light LDL cholesterol and apoB concentrations by 26% (P = 0.005) and 19% (P = 0.03), respectively. In contrast, dense LDL (density = 1.036-1.063 g/mL) cholesterol and apoB concentrations were unchanged by the intervention, as both the apoB fractional catabolic rate and production rate were significantly increased by similar amounts, 39% (from 0.41 to 0.57 pools/day, P = 0.01) and 38% (from 434 to 601 mg/day; P = 0.003), respectively. Estrogen decreased the predominant LDL peak particle size from 273 to 268 A (P = 0.04). Thus, estrogen therapy increases the clearance of both light and dense LDL, counteracting increases in production rates. The reduced plasma residence times of light and dense LDL both may be antiatherogenic, even though, for dense LDL, the concentration did not change.

Relationship between serum estradiol levels and the increases in high-density lipoprotein levels in postmenopausal women treated with oral estradiol.

Postmenopausal women are prescribed a standard dose of estrogen, which is optimal for a population but not for all individuals. We wished to identify if an individual's estradiol level can indicate the minimum effective dose of estrogen which maximally increases high-density lipoprotein (HDL) levels, which could be cardioprotective. We performed a prospective, double-blind crossover study in 19 healthy postmenopausal women, receiving three treatments in random order for 9 weeks each: a) placebo, b) 1 mg oral estradiol daily, and c) 2 mg oral estradiol daily. Lipoprotein and estradiol (E2) levels were measured 10-12 h after pills were taken. E2 levels with 1 mg estradiol were positively correlated with the increases in HDL levels (r = 0.70, P < 0.01). Only the eight subjects who had E2 levels < 50 pg/mL after 1 mg estradiol treatment demonstrated further increases in HDL levels by increasing the daily dose to 2 mg (by 3 +/- 5% with 1 mg estradiol and by 13 +/- 7% with 2 mg). The other 11 subjects who had E2 levels > 50 pg/mL with 1 mg estradiol had no additional benefit from increasing the estradiol dose (HDL increased by 13 +/- 9% with 1 mg, and by 17 +/- 10% with 2 mg). Thus, measurement of an E2 level the morning after taking 1 mg estradiol at bedtime identifies who may benefit from improvement in HDL levels by increasing to a 2-mg dose.

Estradiol with or without progesterone and ambulatory blood pressure in postmenopausal women.

The purpose of this study was to determine whether transdermal estradiol and intravaginal progesterone given in doses to mimic the premenopausal state would lower blood pressure (BP) in postmenopausal women. Fifteen healthy postmenopausal women were studied in each of 3 conditions: on placebo, after 8 weeks of transdermal estradiol 0.2 mg twice per week, and again 2 weeks after addition of intravaginal progesterone 300 mg/d. Women were studied at each point after 2 days of 100 mmol/d sodium intake. Twenty-four-hour ambulatory BP monitoring was performed, and blood was assayed for estradiol, progesterone, and hormones of the renin-angiotensin-aldosterone system (RAAS). ANOVA with pairwise comparisons was used for analysis. Urinary sodium excretion was similar at each time point. Levels of estrogen and progesterone similar to those in premenopausal women were achieved. On estradiol, nocturnal systolic BP (110+/-3 mm Hg), diastolic BP (63+/-2 mm Hg), and mean BP (77+/-2 mm Hg) fell significantly (P<0.02) compared with placebo systolic BP (116+/-2 mm Hg), diastolic BP (68+/-2 mm Hg), and mean BP (82+/-2 mm Hg). Daytime BP followed the same trend but was significantly lower only for mean BP. There was no activation of the RAAS. The addition of progesterone resulted in no further fall in BP but a significant activation of the RAAS. Thus, contrary to what is often assumed, administration of estradiol with or without progesterone not only did not raise BP but rather substantially lowered BP. This BP-lowering effect may be responsible for the lower incidence of hypertension in premenopausal than in postmenopausal women.

Metabolism of Apo(a) and ApoB100 of lipoprotein(a) in women: effect of postmenopausal estrogen replacement.

The metabolism in plasma of apo(a) and apoB100, the major protein components of lipoprotein(a) [Lp(a)], and the mechanism by which estrogen lowers Lp(a) concentration are both not well understood. Estrogen or placebo were administered to 12 postmenopausal women in a double-blind cross-over design; and after each treatment, apo(a) and apoB100 in Lp(a) were endogenously labeled by i.v. trideuterated leucine. After estrogen treatment, mean Lp(a) concentration decreased during estrogen, from 25 mg/dL, by 20% (P < 0.01); and the mean production rate of apo(a) decreased, from 0.31 nmol/kg.day, by 34% (P = 0.046). In contrast, the mean fractional catabolic rates of apo(a) were similar, 0.36 vs. 0.31/day (P = 0.23). In 6 women, the kinetics of apo(a) and apoB100, the two major proteins of Lp(a), were studied during estrogen and placebo periods. During both periods, the rate of appearance of tracer was similar in Lp(a)-apo(a) and Lp(a)-apoB100, as were the resulting metabolic rates and the changes during estrogen treatment. In conclusion, the findings are more compatible with intracellular synthesis of Lp(a) from nascent apo(a) and apoB100 than extracellular assembly from plasma low-density lipoproteins. Reduced flux into plasma of Lp(a), an atherogenic lipoprotein, could contribute to the lower cardiovascular disease rates in women receiving estrogen replacement therapy.

Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease.

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.

The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial.

C-Reactive protein and homocysteine are independent risk factors for the development of cardiovascular disease. This study compared the effects of hormone replacement therapy (HRT) and raloxifene on serum C-reactive protein and homocysteine levels as markers of cardiovascular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, placebo-controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo for 6 months. C-Reactive protein and homocysteine were measured in baseline and 6-month serum samples. HRT increased C-reactive protein levels by 84% (P<0.001), whereas raloxifene (60 and 120 mg/day) had no significant effect (-6% and -4%;, respectively; P>0.2). Raloxifene (60 and 120 mg/day) significantly lowered serum levels ofhomocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained with HRT. We conclude that HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women. Whereas cardiovascular risk predicted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.

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.

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women.

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.

Patterns of contagion in self-mutilation epidemics.

Contagion of self-mutilation was studied in a treatment program for disturbed adolescents. Statistical analyses and a sociogram revealed that 1) episodes of contagion were significantly associated with specific pairs of subjects, and 2) a few subjects were identified as being at the center of most of the contagion activity.

Self-mutilation and contagion: an empirical test.

Twenty-five subjects treated at a center for disturbed adolescents were observed over a 1-year period for signs of self-mutilative contagion. Statistical analysis confirmed that self-mutilation occurred in clusters throughout the year, suggesting that subjects imitated one another's behavior.

Coagulation activation following estrogen administration to postmenopausal women.

We investigated coagulation system activation following estrogen treatment in 29 healthy postmenopausal women. Study participants received conjugated estrogens at 0.625 and 1.25 mg per day, and placebo for 3-month periods in a randomized crossover protocol. Blood samples were obtained on two consecutive days at the end of each treatment period for immunoassays of F1+2 and fibrinopeptide A (FPA), markers of factor Xa action on prothrombin and thrombin action on fibrinogen in vivo, respectively. Treatment with estrogens at a dose of 0.625 or 1.25 mg resulted in significant increases in mean F1+2 levels of 40 and 98%, respectively, and in mean FPA levels of 37 and 71%, respectively. The measurements of F1+2 were significantly higher in women receiving 1.25 mg of estrogen than 0.625 mg. We also observed significant declines in the levels of antithrombin III and total protein S antigen. Immunologic levels of protein C increased modestly at only the 1.25 mg estrogen dose level. These data indicate that low doses of oral estrogens (< or = 1.25 mg per day) frequently increase the amount of thrombin generated in vivo. Our observations may help to explain the increased thrombotic risk that has been observed with higher doses of this medication (> or = 2.5 mg).

The effects of estrogen and selective estrogen receptor modulators on cardiovascular risk factors.

Raloxifene, a selective estrogen receptor modulator, favorably alters several markers of cardiovascular risk in healthy postmenopausal women. While many of its effects are similar to those of conventional hormone replacement therapy (HRT), there are also important differences. Raloxifene lowered low-density lipoprotein cholesterol levels similarly to estrogen. However, raloxifene lacked the potentially beneficial effects of HRT on high-density lipoprotein cholesterol levels and plasminogen activation inhibitor-1, as well as the potentially adverse effects of HRT on triglycerides and C-reactive protein. Raloxifene also had a potentially beneficial fibrinogen-lowering effect not seen with conventional HRT. The net effect of these differences is unclear. Proof that raloxifene or HRT reduces the risk of heart disease must await the results of ongoing clinical trials with cardiovascular event end points.

Differential effects of estrogen on low-density lipoprotein subclasses in healthy postmenopausal women.

The use of estrogen by postmenopausal women decreases plasma low-density lipoprotein (LDL) cholesterol levels. To determine whether LDL subclass profiles influence this response, we studied 31 healthy postmenopausal women who were administered two doses (0.625 and 1.25 mg/d) of conjugated equine estrogen in a placebo-controlled double-blind crossover study. Lipid-stained gradient gels were used to categorize LDL subclass patterns. All women were classified as LDL subclass pattern A (predominant LDL peak > or = 260 A). Within the pattern A classification, there were 12 women during placebo treatment with LDL subclass I pattern (predominant LDL peak > 271 A) and 19 women with LDL subclass II pattern (predominant LDL peak < or = 271 and > or = 260 A). Postmenopausal women with LDL subclass I on placebo treatment had significantly lower LDL cholesterol levels compared with women having LDL subclass II (126 +/- 28 v 147 +/- 23 mg/dL, P < .03). Postmenopausal women with LDL subclass I also had significantly (P < .05) lower very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, and VLDL apo B levels and significantly higher (P < .05) high-density lipoprotein 2 (HDL2) cholesterol, HDL3 cholesterol, and HDL2 apo A-I levels. Estrogen replacement significantly (P < .05) decreased LDL cholesterol levels and increased VLDL and LDL triglyceride, HDL2 and HDL3 cholesterol and apo A-I, and HDL2 apo A-II levels to a similar extent in postmenopausal women with LDL I or II subclass patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium.

OBJECTIVE: To determine the effects of a selective estrogen receptor modulator, raloxifene, on postmenopausal endometrium. METHODS: Healthy postmenopausal women (n = 415) were randomly assigned to one of the following four groups: 60 or 150 mg/day raloxifene hydrochloride, 0.625 mg/day conjugated equine estrogens, or placebo, and treated for 1 year. Endometrial biopsies were obtained in a blinded fashion at baseline and every 6 months after the ultrasound studies. Transvaginal ultrasound, with uterine size measurements, was done at baseline and at 3-month intervals. Saline-infusion sonohysterography was done at baseline and every 6 months. RESULTS: There were no statistically significant differences in baseline characteristics. Mean endometrial thickness, measured by transvaginal ultrasound, was unchanged from baseline to end point in the placebo and raloxifene groups, whereas in the estrogen group it was significantly thicker by 5.5 mm (P < .001). Mean uterine volume, calculated from transvaginal ultrasound measurements, was higher in the estrogen group only (22 cm3, P < .001). Of the 358 women with paired biopsies, endometrial hyperplasia was present in 2.1%, 0%, and 26.1% of the end-point biopsies in the placebo, raloxifene, and estrogen groups, respectively (P < .001). Proliferative endometrium was present in 2.1% of the end-point biopsies in the placebo group, 1.7% in the combined raloxifene groups, and 39.8% in the estrogen group (P < .001). CONCLUSION: Raloxifene, at 60 or 150 mg/day for 1 year, did not stimulate the postmenopausal endometrium. End-point endometrial thickness, morphology, and uterine volume in the raloxifene groups were similar to those observed at baseline and in the placebo group.

Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison.

OBJECTIVE: To compare the clinical efficacy and safety of a thermal uterine balloon system with hysteroscopic rollerball ablation in the treatment of dysfunctional uterine bleeding. METHODS: Two hundred fifty-five premenopausal women were treated in a randomized multicenter study comparing thermal uterine balloon therapy with hysteroscopic rollerball ablation for the treatment of menorrhagia. Preprocedural and postprocedural menstrual diary scores and quality-of-life questionnaires were obtained. Twelve-month follow-up data are presented on 239 women. RESULTS: Twelve-month results indicated that both techniques significantly reduced menstrual blood flow with no clinically significant difference between the two groups as reflected by return to normal bleeding or less (balloon 80.2% and rollerball ablation 84.3%). Multiple quality-of-life questionnaire results were also similar, including percent of patients highly satisfied with their results (balloon 85.6% compared with rollerball 86.7%). A 90% decrease in diary scores was seen in more than 60% of patients in both groups. Procedural time was reduced significantly in the uterine balloon therapy group. Intraoperative complications occurred in 3.2% of the hysteroscopic rollerball patients, whereas no intraoperative complications occurred in the thermal balloon group. CONCLUSION: In the treatment of dysfunctional uterine bleeding, uterine balloon therapy is as efficacious as hysteroscopic rollerball ablation and may be safer.

Acute adrenocorticotropin stimulation of postmenopausal cigarette smokers and nonsmokers: effects on steroidogenesis.

Cigarette smoking has been associated with elevated levels of A and DHEAS in postmenopausal women. One possible mechanism postulated for this effect is enzymatic blockage by components of cigarette smoke. In this study, acute ACTH stimulation of postmenopausal cigarette smokers did not result in abnormal elevations of precursor steroids. Other possible mechanisms may be operative in vivo to account for the previously reported findings.

The effects of ethanol on the clearance of estradiol in postmenopausal women.

OBJECTIVE: To determine whether acute alcohol ingestion affects the pattern of decline of circulating E2 levels after removal of transdermal E2 patches. DESIGN: A randomized, placebo-controlled, crossover study. SETTING: The study was performed in the Clinical Research Center of the Brigham and Women's Hospital. PARTICIPANTS: Twelve healthy postmenopausal women were enrolled. INTERVENTIONS: Transdermal E2 patches, 0.15 mg, were applied 13 hours before subjects ingested alcohol (1 mL/kg 95% ethanol) or carbohydrate placebo punch. The patches were removed immediately after drink ingestion. MAIN OUTCOME MEASURES: Estradiol, estrone (E1), and ethanol levels were measured. RESULTS: Serum samples were obtained for 40 minutes before drink ingestion and 5 hours after drink ingestion and E2 patch removal. At the time of patch removal, E2 levels rose acutely over 10 minutes and then decreased rapidly, suggesting a bolus effect that was more marked after ethanol ingestion. After ethanol ingestion and patch removal the half-life of E2 was calculated to be 378 minutes, and after carbohydrate punch and patch removal 245 minutes. There were no significant changes in E1 concentrations over the time course of the study between groups. CONCLUSIONS: Ethanol ingestion may decrease E2 clearance after removal of transdermal E2 patches.