Effects Of Transdermal Estradiol Research Articles

Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.

Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. Double-blind, randomized, placebo-controlled 12-month longitudinal study. Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.

The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomised breast cancer chemoprevention trial

The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomised breast cancer chemoprevention trial

Quality of life assessment in a chemoprevention trial: Fenretinide and oral or transdermal HRT

Background Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) relief menopause symptoms, but may increase breast cancer risk, while the effects of transdermal estradiol (E2) and MPA are less known. In previous studies, fenretinide decreased second breast malignancies in premenopausal but not in postmenopausal women, suggesting a hormone-sensitizing effect. We have evaluated the quality of life through a self-administered questionnaire during a randomized study of oral CEE or transdermal E2 and fenretinide or placebo. Methods A total of 226 postmenopausal women were randomly assigned to either CEE 0.625 mg/day and placebo ( n = 55), or CEE and fenretinide 100 mg/bid ( n = 56), or E2, 50 μg/day and placebo ( n = 59), or E2 and fenretinide ( n = 56) for 12 months. Sequential MPA 10 mg/day was added in all groups. Treatment effects were investigated using a validated questionnaire, the Menopause Quality of Life questionnaire (MENQOL). Results Oral CEE and transdermal E2 have a comparable activity in reducing menopausal symptoms ( p = ns). Both routes ameliorate significantly the symptoms after 1 year of treatment ( p < 0.0001). Fenretinide does not modify the effects of hormonal replacement therapy. Conclusions Oral CEE and transdermal E2 have similar effect on menopausal symptoms relief. The choice of the best estrogen replacement therapy (ERT) route should be decided based on a careful analysis of all the clinical aspects of every subject, considering that transdermal therapy may have a safer effect on the cardiovascular system.

The effects of transdermal estradiol alone or with cyclical dydrogesterone on markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes: a pilot study.

The objective of this open, longitudinal, controlled study was to assess the effect of transdermal estradiol alone or combined with cyclical dydrogesterone on the markers of cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes. The control group consisted of postmenopausal diabetic women who declined menopausal hormone replacement therapy (HRT). Twenty-eight postmenopausal women (19 on HRT and 9 controls) with type 2 diabetes were followed up for 12 months. From the active treatment group 14 women with a uterus in situ had 80 microg/24 hr transdermal estradiol (Fematrix 80; Solvay Healthcare Ltd, Southampton, UK) and oral dydrogesterone 10 mg daily for the first 12 days of the calendar month, whereas 5 women with previous hysterectomy had 80 microg/24 hr transdermal estradiol (Fematrix 80) alone. CVD risk markers were measured before and at regular intervals after starting HRT. The main outcome measures were weight, systolic and diastolic blood pressure, fasting plasma glucose, glycated hemoglobin (HbA1c), glucose/insulin ratio, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein (a), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and endothelin-1. Transdermal estradiol with or without dydrogesterone in women with type 2 diabetes did not adversely affect any of the measured markers of cardiovascular risk. There was a significant decrease in HbA1c, total cholesterol, and LDL cholesterol at 6 months in women receiving HRT. Some of the cardiovascular disease risk markers may improve in postmenopausal women with type 2 diabetes with transdermal estradiol. This effect may have important clinical implications and it deserves further investigation in appropriately designed trials.

Effect of Transdermal Estradiol and Oral Conjugated Equine Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women

To the Editor: In their interesting study, Decensi et al1 demonstrated that oral conjugated equine estrogen caused an increase in plasma C-reactive protein (CRP), whereas transdermal estradiol (E2) did not elevate CRP levels. The Heart and Estrogen/Progestin Replacement Study (HERS) and Women’s Health Initiative (WHI) trials demonstrated that oral hormone replacement therapy (HRT) did not reduce the risk of coronary artery disease (CAD) in postmenopausal women with or without coronary disease. Because elevated CRP is an independent risk factor for cardiovascular disease, a proinflammatory effect of oral estrogen might explain the increased risk of CAD during the first year of these recent trials. Accordingly, neutral effect of transdermal E2 on CRP might possibly be associated with a safer profile on early CAD risk. However, it is not clear whether oral estrogen stimulates systemic inflammatory responses or whether it simply stimulates hepatic synthesis of …

The Effects of Transdermal Estradiol in Combination with Oral Norethisterone on Lipoproteins, Coagulation, and Endothelial Markers in Postmenopausal Women with Type 2 Diabetes: A Randomized, Placebo-Controlled Study

The Effects of Transdermal Estradiol in Combination with Oral Norethisterone on Lipoproteins, Coagulation, and Endothelial Markers in Postmenopausal Women with Type 2 Diabetes: A Randomized, Placebo-Controlled Study

The Effects of Transdermal Estradiol in Combination with Oral Norethisterone on Lipoproteins, Coagulation, and Endothelial Markers in Postmenopausal Women with Type 2 Diabetes: A Randomized, Placebo-Controlled Study

People with type 2 diabetes have a substantially increased risk of coronary heart disease (CHD). Short-term studies with unopposed oral estradiol in women with diabetes have suggested potentially beneficial effects on lipids, thrombotic factors, and insulin sensitivity. However, most (nonhysterectomized) postmenopausal women require combined estrogen-progesterone preparations. We randomized 43 women with type 2 diabetes either to continuous transdermal estradiol (80-microg patches) in combination with oral norethisterone (1 mg daily) or to identical placebos. Blood samples were taken before and after 6 months for measurement of lipoproteins, coagulation factors, and endothelial markers. Total cholesterol and triglyceride concentrations decreased by 8% and 22%, respectively, in those receiving hormone replacement therapy (P < 0.05 relative to change in placebo group after adjustment for baseline concentrations). There was a trend toward a reduction in high density lipoprotein cholesterol concentration (P = 0.06). Factor VII activity decreased by 16% (P < 0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, lipoprotein(a), and leptin were not significantly altered. No change in glycemic control was detected. Overall, lipid changes may be considered slightly beneficial with respect to CHD risk. The significant decrease in factor VII activity in this study is notable, because elevated factor VII activity has been associated with an increased risk of coronary thrombosis and normally increases with administration of oral estrogen-containing preparations. In addition, a reduction in von Willebrand factor antigen is consistent with an improvement in endothelial function. We suggest that the regimen used in this study may have the potential to reduce CHD risk in women with type 2 diabetes.

Lack of effects of transdermal estradiol on diastolic function: a randomized placebo-controlled double-blind short-term trial

Objective Limited information is available on the effects of transdermal estradiol on diastole. The present study was a randomized double-blind placebo-controlled trial designed to investigate the short-term effects of transdermal estradiol on left ventricular diastolic function in postmenopausal women.Methods The study included 45 women aged 50.8 ± 3.6 years (25 randomized to the study group and 20 to placebo), who underwent Doppler echocardiography and determination of the plasma estradiol level after 4 and 8 weeks of transdermal estradiol administration in a dose of 50 μg per 24 h.Results There were no modifications in heart rate. Systolic blood pressure dropped in the study patients after 8 weeks (p < 0.03); diastolic blood pressure remained unchanged. Estradiol levels were 67 ± 36 pg/ml at 4 weeks and 70 ± 49 pg/ml at 8 weeks in the study group. Basal values of peak early and peak atrial velocities, acceleration time and rate, deceleration time and rate, early/atrial velocity ratio and pressure half-time were not significantly different between the estradiol and placebo groups. Doppler values remained unchanged after both 4 and 8 weeks in women receiving estradiol. Women with relatively high serum 17β-estradiol levels (> 100 pg/ml) at 4 or 8 weeks of treatment did not present more pronounced changes in the Doppler-derived parameters compared with patients with low hormone levels.Conclusion The results showed a lack of short-term effects of transdermal estradiol on left ventricular diastolic function in postmenopausal women, irrespective of serum estradiol levels.

The influence of medroxyprogesterone acetate on the effects of transdermal oestradiol replacement therapy on plasma lipids

A prospective study was carried out on 82 healthy menopausal women to determine whether or not there is an attenuation of the cardioprotective effects of continuous transdermal oestradiol on plasma lipid and lipoprotein concentrations with the use of sequential oral medroxyprogesterone acetate. Group 1 comprised 51 hysterectomised women on transdermal oestradiol (50 mug daily). Group 2 included 31 women with an intact uterus on oestradiol (50 mug daily) and medroxyprogesterone acetate (10 mg daily for the first 12 days of each calendar month). Women maintained on 50 mug throughout 6 months (group 1: n = 29; group 2: n = 20) were reviewed for changes in plasma lipids and lipoproteins at the end of 6 months (group 1), and in the combined phase of treatment in the seventh month (group 2). In group 1, there was a reduction in the concentrations of total cholesterol (- 6.3%, P = 0.004) and LDL-cholesterol (- 6.1%, P = 0.05). In group 2, there were no significant changes in total cholesterol (- 4.8%, P = 0.23) and LDL-cholesterol (- 5.8%, P = 0.30). HDL-cholesterol levels did not change significantly with unopposed oestradiol (+ 3.8%, P = 0.30), or with additional medroxyprogesterone acetate (0%, P = 0.94). Serum triglyceride concentrations decreased significantly in both the groups (- 14.3%, P = 0.001, and- 12.8%, P = 0.006, respectively). There were no statistically significant differences in the changes in the respective plasma lipid parameters on comparing the two treatment groups ( P 0.4 for all comparisons, Student's t -tests). The plasma lipid and lipoprotein profile encountered at the end of 6 months, was also generally maintained in 24 women (group 1: n = 13; group 2: n = 11) who completed 1 year of the study. Transdermal oestradiol may be of particular clinical benefit for women with hypertriglyceridaemia. Medroxyprogesterone acetate did not exert a significantly adverse influence on plasma lipid and lipoprotein concentrations.

The effect of transdermal estradiol on the conjunctiva in postmenopausal women

Objective: To evaluate the effect of hormonal replacement therapy on the conjunctiva in postmenopausal women. Study design: A prospective clinical study in the setting of a tertiary-care university hospital. Eleven postmenopausal women received hormonal replacement therapy (transdermal estradiol or transdermal estradiol plus medroxyprogesterone acetate) for 4 months. Serum estradiol levels as well as vaginal and conjunctival maturation value (a cytological parameter) were measured before and after the treatment. Data were analysed using the Wilcoxon matched pairs signed-Rank test. Results: A significant increase of serum estradiol levels ( P < 0.01) and of vaginal maturation value ( P < 0.01) were found. Cytological maturation changes in conjunctival epithelium were also observed. These changes, although mild, were statistically significant ( P < 0.01). Conclusion: These data support the view that the hormonal replacement therapy induces cytological maturation changes in conjunctival epithelium in postmenopausal women.

F222 Antiresorptive effect of transdermal estradiol on bone mass in healthy, osteoporotic and fractured postmenopausal women

F222 Antiresorptive effect of transdermal estradiol on bone mass in healthy, osteoporotic and fractured postmenopausal women

Effects of transdermal estradiol on serum lipids/lipoproteins and glucose tolerance in postmenopausal hypercholesterolemic women.

Effects of transdermal estradiol on serum lipids/lipoproteins and glucose tolerance in postmenopausal hypercholesterolemic women.

Effects of transdermal estradiol on bone metabolism in prevention and therapy of postmenopausal osteoporosis: A 1-year case-controll study

Effects of transdermal estradiol on bone metabolism in prevention and therapy of postmenopausal osteoporosis: A 1-year case-controll study

The Effects of Transdermal Estradiol and Oral Conjugated Estrogens on Haemostasis Variables

The effects of oral and transdermal administration of estrogen replacement therapy (ERT) have been fairly well investigated regarding lipoprotein and carbohydrate metabolism, while the effects of different modes of estrogen administration on the haemostatic system have been less well studied. To delineate and compare the effects of perorally administered conjugated estrogens (CE) and transdermally administered estradiol (E2) in doses needed for hormone replacement therapy (HRT) on haemostasis parameters, 23 postmenopausal women were engaged in a study with an open cross-over design. The doses compared (0.625 mg CE and 50 micrograms E2/24h) are the lowest which, with few exceptions, eliminate climacteric symptoms. Both CE and E2 increased factor VII:C, factor VII:Ag, and the prothrombin fragment1 + 2. The increase in factor VII:Ag, however, was significantly higher after treatment with CE. These changes were all towards a state of hypercoagulability. Furthermore, CE decreased plasminogen activator inhibitor (PAI) and the thrombin-antithrombin complexes (TAT), as well as antithrombin (ATIII).

Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: A double-blind placebo-controlled study

The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a randomized trial over 12 weeks. Two hundred forty-two women were randomized, and 223 were analyzed for efficacy (n = 112 for estradiol and n = 111 for placebo). The quality of life was assessed by means of a battery of standard questionnaires. Quality of life improved after both therapies, but health-related quality of life (p = 0.0003) and well being (p = 0.003) improved more after transdermal estradiol therapy than after placebo. This was also the case for all specific climacteric aspects, including sexual problems (p < 0.0001) and dysfunction (p = 0.01), at comparison with placebo. Self-rated symptom relief was more pronounced with estrogen therapy than with placebo (p < 0.0001). It was concluded that estradiol therapy was superior to placebo in relieving symptoms and improving quality of life.

92215525 Endometrial effect of transdermal estradiol and progestin ST-1435 in postmenopausal women

92215525 Endometrial effect of transdermal estradiol and progestin ST-1435 in postmenopausal women

Cardiovascular Effects of Transdermal Estradiol in Postmenopausal Women

Cardiovascular Effects of Transdermal Estradiol in Postmenopausal Women

Biologic Effects of Transdermal Estradiol

We conducted a dose-response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 micrograms of transdermal estradiol per 24 hours, and 0.625 and 1.25 mg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 micrograms of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins.