Raloxifene lowers serum lipoprotein(A) in healthy postmenopausal women: a randomized, double-blind, placebo-controlled comparison with conjugated equine estrogens.

OBJECTIVE: Long-term postmenopausal estrogen replacement therapy lowers the risk of osteoporotic fractures and coronary artery disease but increases the risk of endometrial cancer and probably breast cancer. Raloxifene, a nonsteroidal estrogen receptor ligand, seems to have a tissue-specific antiestrogenic action on endometrium and breast and the desired estrogenic action on bone and lipid metabolism. The purpose of this study was to investigate the effects of 24-month treatment with orally administered raloxifene in two doses (60 mg and 150 mg daily) and conjugated equine estrogens in a standard oral dose (0.625 mg daily) on serum lipoprotein(a) [Lp(a)], an independent risk factor for coronary artery disease, in healthy postmenopausal women who had undergone hysterectomy. DESIGN: A randomized, double-blind, placebo-controlled study was performed with 56 women. RESULTS: In the placebo group serum Lp(a) levels did not change throughout the study. After 6 months, serum Lp(a) was significantly reduced versus baseline in the raloxifene 150 (-17%; p = 0.003) and conjugated equine estrogens (-26%; p = 0.003) groups, but this reduction was significantly different from placebo only in the conjugated equine estrogens group. At 12 and 24 months, serum Lp(a) levels were significantly lowered versus baseline in all active treatment groups. However, these reductions were significantly different from placebo only in the raloxifene 150 and conjugated equine estrogens groups. After 24 months, serum Lp(a) was reduced versus baseline with 30% (p = 0.001) in the raloxifene 150 group and 35% (p = 0.001) in the conjugated equine estrogens group. CONCLUSIONS: Long term raloxifene treatment significantly lowers serum Lp(a) levels in postmenopausal women and thus might reduce the risk of coronary artery disease.     

Effects of transdermal and oral postmenopausal hormone therapy on vascular function: a randomized, placebo-controlled study in healthy postmenopausal women

OBJECTIVE: To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women. DESIGN: In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 microg of transdermal 17ss-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 microg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness). RESULTS: Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P < 0.01; oE2+ G, P < 0.001), sE-selectin (oE2 + G, P < 0.05), von Willebrand factor (tE2, P < 0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery. CONCLUSIONS: Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive.     

The effect of synthetic genistein on menopause symptom management in healthy postmenopausal women: a multi-center, randomized, placebo-controlled study

Objective

To evaluate the efficacy of synthetic genistein for reducing the frequency and severity of hot flushes.

Study design

A 12 week randomized double-blind, placebo-controlled study in which 84 postmenopausal women received placebo or a single 30 mg dose of synthetic genistein.Outcome measures primary: percentage change in the number of daily hot flushes from pre-treatment to week 12. Secondary: duration and severity of daily hot flushes, Greene Climacteric Scale score, serum follicle stimulating hormone (FSH), 17β-estradiol and endometrial thickness.

Results

Genistein supplemented subjects completing at least 4 weeks on trial (n = 40) demonstrated a 51% reduction (9.4–4.7/day) in the number of hot flushes by week 12 compared to a 27% reduction in the placebo group (9.9–7.1/day) (p = 0.026). Subjects in the genistein group also reported significantly fewer hot flushes per day (p = 0.010) and a decrease in total duration of hot flushes per day (p = 0.009) at week 12 versus placebo. Subjects on genistein (n = 32) completing 12 weeks on trial demonstrated a 51% reduction (9.7–4.7/day) in the number of hot flushes by week 12 (p = 0.049) compared to 30% reduction in the placebo group (9.8–7.0/day) and had fewer hot flushes per day and a decrease in total duration of hot flushes per day at week 12 compared to placebo (p = 0.020 and p = 0.017, respectively). There were no differences between groups in Greene Climacteric Scale, FSH, 17β-estradiol, endometrial thickness or adverse events.

Conclusions

The current study provides the first evidence that a single daily dose of 30 mg of synthetic genistein reduces hot flush frequency and duration.     

Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study

OBJECTIVE: We evaluated and compared the effects of the phytoestrogen genistein, estrogen-progestogen therapy (EPT), and placebo on hot flushes and endometrial thickness in postmenopausal women. DESIGN: Ninety healthy, postmenopausal women, 47 to 57 years of age, were randomly assigned to receive for 1 year continuous EPT (n = 30; 1 mg 17beta-estradiol combined with 0.5 mg norethisterone acetate), the phytoestrogen genistein (n = 30; 54 mg/day), or placebo (n = 30). Endometrial safety was evaluated by intravaginal ultrasounds at baseline, 6 and 12 months. RESULTS: By comparison with placebo, daily flushes reduced significantly by a mean of 22% (95% CI: -38 to -6.2; P < 0.01) after 3 months, by a mean of 29% (95% CI: -45 to -13; P < 0.001) after 6 months, and by a mean of 24% (95% CI: -43 to -5; P < 0.01) after 12 months of genistein treatment. Flush score decreased by a mean of 53% (95% CI: -79 to -26; P < 0.001) after 3 months, by a mean of 56% (95% CI: -83 to -28; P < 0.001) after 6 months, and by a mean of 54% (95% CI: -74 to -33; P < 0.001) after 12 months of EPT, as compared with placebo. No side effect was observed on the uterus of the participants. CONCLUSIONS: The present study confirms that genistein might have positive effects on hot flushes without a negative impact on endometrial thickness and suggests a future role of this phytoestrogen as a strategically therapeutic alternative in the management of postmenopausal symptoms.     

Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: A randomized,double-blind,placebo-controlled study

Background

Vaginal atrophy, the thinning and drying of vaginal mucosa, is associated with menopause. The standard estrogen treatment is not suitable for all women.

Objective

To investigate the effects of oral sea buckthorn (SB) oil supplementation on vaginal atrophy.

Method

A total of 116 postmenopausal women experiencing symptoms of vaginal dryness, itching or burning were randomized to this placebo-controlled, double-blind study. Ninety-eight participants completed the intervention of three months, during which they consumed 3 g of SB or placebo oil daily. At the beginning and end, factors of vaginal health were scored by a gynecologist, vaginal pH and moisture were measured and vaginal health index was calculated. Symptoms of atrophy and menopause were evaluated at study visits and by daily logbooks. Serum samples were collected for the analysis of circulating lipids, liver enzymes and C-reactive protein.

Results

Compared to placebo, there was a significantly better rate of improvement in the integrity of vaginal epithelium in the SB group when both compliant and noncompliant participants were included (odds ratio (OR) = 3.1, 95% CI 1.11–8.95). A beneficial trend was observed when only the compliant participants were included (OR = 2.9; 95% CI 0.99–8.35). There was a tendency (P = 0.08) toward better improvement of vaginal health index from baseline to the end in the SB group [(0.8 (SD 2.8)] compared to placebo [−0.1 (SD 2.0)].

Conclusions

SB oil showed beneficial effects on vaginal health, indicating it is a potential alternative for mucosal integrity for those women not able to use estrogen treatment for vaginal atrophy.     

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate in a 12-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium. DESIGN: A total of 389 participants met the main study criteria and were randomly assigned to receive the phytoestrogen genistein (n=198) or placebo (n=191). About 40% of participants in both groups did not suffer from hot flushes, and the evaluation was performed in a subgroup of 247 participants (genistein, n=125; placebo, n=122). Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS: There were no significant differences in age, time since menopause, body mass index, and vasomotor symptoms between groups at baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). The effect was already evident in the first month and reached its peak after 12 months of genistein therapy (-56.4% reduction in the mean number of hot flushes). Furthermore, there was a significant difference between the two groups at each evaluation time (1, 3, 6, and 12 months). No significant difference was found in mean endometrial thickness and maturation value score between the two groups, either at baseline or after 12 months. CONCLUSIONS: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium.     

The effect of hormone therapy on serum melatonin concentrations in premenopausal and postmenopausal women: A randomized,double-blind,placebo-controlled study

Objectives

Melatonin levels decrease physiologically with age, and possibly with the transition to menopause. The plausible influence of hormone therapy (HT) on melatonin is poorly understood. The aim of this randomized, placebo-controlled, double-blind trial was to investigate the effect of HT administration on serum melatonin concentrations in late premenopausal and postmenopausal women.

Study design

Analyses were carried out among 17 late premenopausal and 18 postmenopausal healthy women who participated in a prospective HT study in Finland. Serum melatonin was sampled at 20-min (21:00–24:00 h; 06:00–09:00 h) and 1-h (24:00–06:00 h) intervals at baseline and after 6 months with HT or placebo.

Main outcome measures

Melatonin levels and secretion profile after 6 months of HT compared to placebo.

Results

Mean melatonin levels, mean melatonin exposure level (area under curve, AUC) and mean duration of melatonin secretion did not differ after 6 months with HT vs. placebo, irrespectively of the reproductive state. However, in postmenopausal women the melatonin peak time (acrophase) was delayed by 2.4 h (2 h 21 min) on average after 6 months with HT vs. placebo (p < 0.05). No interaction between time and group was detected when melatonin level was modelled before or after treatment.

Conclusions

Administration of HT to postmenopausal women alters melatonin peak time, but not melatonin levels. Further research on larger clinical samples is needed to better understand the effects of HT on melatonin profile.     

A prospective,randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women

OBJECTIVES: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. METHODS: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. RESULTS: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively). CONCLUSION: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.     

Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study

OBJECTIVE: To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women. DESIGN: In this double-blind, randomized, placebo-controlled study, a total of 80 women (mean age = 55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250 mg of standardized soy extract (Glycine max AT) a total of 100mg/day of isoflavone (n = 40) or placebo (n = 40). Exclusion criteria included: contra-indication for hormone therapy (HT), chronic gastrointestinal diseases, and users of HT within the preceding 6-months. For 10-months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured. The t-test, Wilcoxon test and ANOVA were used in the statistical analysis. RESULTS: At baseline, the mean number of hot flushes was 9.6 +/- 3.9 per day in the isoflavone group and 10.1+/-4.9 in the placebo group (p>0.05). After 10 months, there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1 +/- 2.3 and 5.9 +/- 4.3, respectively) (p<0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo, in reducing hot flush severity (69.9% and 33.7%, respectively) (p<0.001). Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups. No serious adverse event related to isoflavone treatment was reported. CONCLUSIONS: The soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance, providing a safe and effective alternative therapeutic for postmenopausal women.     

Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study

OBJECTIVE: To determine the safety and efficacy of an oral soy isoflavone extract for relief of menopausal hot flushes. DESIGN: This was a double-blind, randomized, parallel group, outpatient, multicenter (15 sites) study. A total of 177 postmenopausal women (mean age = 55 years) who were experiencing five or more hot flushes per day were randomized to receive either soy isoflavone extract (total of 50 mg genistin and daidzin per day) or placebo. Physical examinations and endometrial and biochemical evaluations were performed upon admission and completion. Body weight, symptoms, and safety were evaluated at all visits. RESULTS: Relief of vasomotor symptoms was observed in both groups. Decreases in the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy group, whereas the placebo group experienced no relief for the first 4 weeks. Differences between evaluable subjects in both groups were statistically significant over 6 weeks (p = 0.03). Over 12 weeks, between-group differences approached significance (p = 0.08). Endometrial thickness evaluated by ultrasound, lipoproteins, bone markers, sex hormone-binding globulin and follicle-stimulating hormone, and vaginal cytology did not change in either group. CONCLUSIONS: Soy isoflavone extract was effective in reducing frequency and severity of flushes and did not stimulate the endometrium. Soy isoflavone extracts provide an attractive addition to the choices available for relief of hot flushes.     

Efficacy and tolerability of estradiol 1 mg and drospirenone 2 mg in postmenopausal Korean women: a double-blind, randomized, placebo-controlled, multicenter study

Objectives

The aim of this study was to demonstrate that the therapeutic efficacy of an estradiol 1 mg/drospirenone 2 mg (E2/DRSP) preparation is superior to a placebo in postmenopausal Korean women with hot flushes and other climacteric symptoms, and to demonstrate that this treatment is both safe and tolerable.

Methods

This was a double-blind, randomized, placebo-controlled, multicenter study over four 28-day treatment cycles. A total of 158 subjects were screened and 90 women were randomized into two treatment groups (E2/DRSP group, n = 45; placebo group, n = 45). The primary efficacy parameter was the individual relative change of hot flushes. The secondary efficacy parameters such as other climacteric, urogenital symptoms and vaginal bleeding patterns were also evaluated, and the occurrence of any adverse events was noted. In addition, physical, gynecological examinations and laboratory analyses were performed at the beginning and end of the study.

Results

The mean number of hot flushes per week during treatment weeks 3–16 decreased by 48.1% during treatment with placebo, and by 84.4% during treatment with E2/DRSP (p < 0.001). The E2/DRSP combination also reduced the incidence and intensity of menopausal symptoms in postmenopausal women. Most of adverse events was mild or moderate degree of intensity. None of the parameters measured in the study, including laboratory analyses, physical and gynecological examinations, vital signs, and weight, led to any concerns of safety.

Conclusions

The E2 1 mg/DRSP 2 mg combination tested in the study was efficacious and safe in the treatment of hot flushes and other climacteric symptoms in postmenopausal Korean women.     

Effects on asymmetric dimethylarginine of HMR 3339, a novel selective estrogen receptor modulator: a 12-week, randomized, placebo-controlled, double-blind, dose-ranging study in healthy postmenopausal women

OBJECTIVE: To investigate the short-term effects of three different doses of the selective estrogen receptor modulator HMR 3339 in comparison with placebo and raloxifene on asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor. DESIGN: This study was a multicenter, randomized, placebo-controlled, double-blind, dose-ranging study. Ninety-four healthy postmenopausal women received daily doses of either placebo (n=16), HMR 3339 2.5 mg (n=20), HMR 3339 10 mg (n=19), HMR 3339 50 mg (n=20), or raloxifene 60 mg (n=19) for 12 weeks. Fasting plasma concentrations of ADMA, arginine, and symmetric dimethylarginine (SDMA) were measured at baseline and after 4 and 12 weeks by high-performance liquid chromatography. RESULTS: HMR 3339 induced a dose-dependent reduction of ADMA and SDMA concentrations, with the largest effects (P<0.01 for both) in the HMR 3339 50 mg group compared with baseline and placebo (at 12 weeks: -7.0% [95% CI, -14.2% to 0.2%] for ADMA and -16.2% [95% CI, -22.4% to -10.0%] for SDMA). Twelve weeks of raloxifene 60 mg significantly reduced SDMA (P=0.03) but not ADMA concentrations. Arginine concentrations were not altered by any treatment. CONCLUSIONS: The reduction of the nitric oxide synthase inhibitor ADMA by HMR 3339 may potentially have a beneficial effect on the cardiovascular system in postmenopausal women.     

A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women

OBJECTIVE: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on parameters of quality of life. However, because of known or suspected serious side-effects of conventional hormone therapy there is a need for alternatives. DESIGN: We conducted a double-blind randomized placebo-controlled trial with soy protein, containing 52 mg genistein, 41 mg daidzein, and 6 mg glycitein (aglycone weights), or milk protein (placebo) daily for 1 year. For this trial, we recruited 202 postmenopausal women aged 60 to 75 years. RESULTS: At baseline and at final visit, participants filled in the Short Form of 36 questions (SF-36), the Questionnaire on Life Satisfaction Modules (QLS(M)), and the Geriatric Depression Scale (GDS). For the placebo group scores on all dimensions of the SF-36 and the QLS(M) decreased during the intervention year, except for the dimension "role limitations caused by physical problems." The soy group showed increases on two dimensions of the SF-36 ("social functioning" and "role limitations caused by physical problems") and on one dimension of the QLS(M). There were however no statistically significant differences in changes of scores between the two intervention groups. For the GDS similarly, no significant differences were found between the groups. CONCLUSIONS: In conclusion, the findings in this randomized trial do not support the presence of a marked effect of soy protein substitution on quality of life (health status, life satisfaction, and depression) in elderly postmenopausal women.     

Immunotherapy with an alum-adsorbed Parietaria-pollen allergoid: a 2-year, double-blind, placebo-controlled study

A double-blind, placeo-controlled study was performed in order to confirm the safety, suitability, and efficacy of an alum-adsorbed Parietaria judaica -pollen allergoid, Allergovit®, for allergen-specific immunotherapy. Parietaria pollen is an important cause of pollinosis, particularly in the Mediterranean zone, where it may be encountered for up to 8–9 months of the year. It is an aggressive allergen, and the doses tolerated during immunotherapy are less than those achieved with grass pollen. This factor increases the desirability of using therapeutic preparations with minimal IgE-binding activity, such as allergoids, in order to reduce the risk of side-effects and enable patients to tolerate a higher dose of allergen, thereby increasing the chances of successful specific immunotherapy. Forty patients with rhinitis and/or asthma were allocated at random to active- or placebo-treatment groups at the beginning of the study. All patients received the active preparation during the second year of the study. Immunotherapy was well tolerated by all patients and the incidence of side-effects was low. Treatment resulted in significant reductions in specific cutaneous reactivity and increases in nasal tolerance. A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation. These objective assessments of efficacy endorsed the results from the patients' diary cards, which indicated significant improvements in symptoms and reductions in the use of medication. The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific-IgG antibody response, with increases in IgG4 during the second year of treatment. We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria -pollen-induced rhinitis or asthma.     

A 2-year, randomized, comparative, placebo-controlled study on the effects of raloxifene on lipoprotein(a) and homocysteine

OBJECTIVES: Lipoprotein(a) (Lp(a)) and homocysteine (Hcy) are independent cardiovascular risk factors, which have been shown to be lowered by hormone replacement therapy (HRT). In this 2-year study, the long-term effects of raloxifene (Rlx) in two doses, on Lp(a) and Hcy, were studied and compared with the effects of continuously combined hormone replacement therapy (ccHRT). METHODS: In a prospective, randomized, double-blind, placebo-controlled 2-year study, 95 healthy, non-hysterectomized, early postmenopausal women, received daily either oral Rlx 60 mg (N=24) or 150 mg (N=23), ccHRT (conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg; N=24) or placebo (N=24). Fasting serum Lp(a) and plasma Hcy concentrations were measured at baseline and at 6, 12 and 24 months. RESULTS: The mean individual changes compared to baseline after 24 months were for Lp(a): Rlx 60: - 5%, Rlx 150: -7%, ccHRT: -34%, placebo: +1% and for Hcy: Rlx 60: -3%, Rlx 150: -4%, ccHRT: -4%, placebo: +6%. ANCOVA was significant for Lp(a) under ccHRT versus placebo (P=0.001) and for Lp(a) under ccHRT versus each of the two Rlx groups (P<0.05). CONCLUSIONS: Long-term treatment with Rlx was not as effective as ccHRT in lowering Lp(a). Although not significant and without an obvious dose-related response, the Hcy values showed the same trend for each treatment arm, which is in line with data reported earlier.     

Oral, more than transdermal, estrogen therapy improves lipids and lipoprotein(a) in postmenopausal women: a randomized, placebo-controlled study

OBJECTIVE: To assess the effects of low-dose oral and transdermal estrogen therapy on the lipid profile and lipoprotein(a) [Lp(a)] levels in healthy, postmenopausal women and to study the additional influence of gestodene administration. DESIGN: In a multicenter, randomized, double-blind, placebo-controlled study, 152 healthy, hysterectomized, postmenopausal women received daily either placebo (n = 49), 50 microg transdermal 17beta-estradiol (tE2, n = 33), 1 mg oral 17beta-estradiol (oE2, n = 37), or 1 mg oE2 combined with 25 microg gestodene (oE2 + G, n = 33) for 13 cycles of 28 days, followed by 4 cycles of placebo in each group. Fasting serum concentrations of total, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, triglycerides, and Lp(a) were measured at baseline and in cycles 4, 13, and 17. RESULTS: In cycle 13, a significant mean percentage decrease from baseline was found in all treatment groups compared with placebo in total cholesterol (tE2, -4.7%; oE2, -6.9%; oE2 + G, -10.5%) and LDL cholesterol (tE2, -5.8%; oE2, -12.6%; oE2 + G, -13.6%). For both oral groups, the reductions were already significant in cycle 4. None of the treatment groups showed a significant change in HDL cholesterol or triglycerides. In cycle 13, Lp(a) was decreased compared with placebo in the oE2 group (-6.6%) and the oE2 + G group (-8.2%). After washout, all observed changes had returned to baseline level, except for the decreases in total and LDL cholesterol in the oE2 + G group. CONCLUSIONS: Oral E2 and E2 + G, and to a lesser extent transdermal E2, decreased total and LDL cholesterol. Lp(a) was lowered only by the oral treatments.     

The effects of sequential combined oral 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition in healthy postmenopausal women: a randomized single blind placebo-controlled study

OBJECTIVE: The androgenic effect of progestogen, necessary in early postmenopausal hormone replacement therapy (HRT), may adversely affect insulin sensitivity as well as body fat distribution and thereby increase the cardiovascular risk profile. The impact of HRT with sequential combined oral 17beta-estradiol and norethisterone acetate on insulin sensitivity and body composition in early menopause has not been studied. DESIGN: A randomized single blind placebo-controlled 6-month study of sequential combined 17beta-estradiol norethisterone acetate on insulin sensitivity and body composition was carried out. Thirty fit healthy postmenopausal women were enrolled and completed this 6-month study. Body composition was measured by dual-energy x-ray absorptiometry scanning, and insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp. Studies were undertaken at baseline and after 6 months of therapy. The studies were performed during the estrogen-only phase of therapy. RESULTS: All women demonstrated a degree of decreased insulin sensitivity that was not modified by 6 months of hormone replacement therapy. Body composition remained unchanged over 6 months. There was no alteration in total body fat or the distribution of body fat. The percentage of central abdominal fat (android) was not altered. CONCLUSION: Six months of HRT with sequential combined oral 17beta-estradiol norethisterone acetate does not have an adverse effect on insulin sensitivity and does not promote an increase in weight or the more android distribution of body fat, which could contribute to the increased cardiovascular risk profile that is evident in postmenopausal women.