Hormone replacement therapy to improve left ventricular diastolic functions in healthy postmenopausal women.

OBJECTIVES: To investigate the effects of estrogen and estrogen plus progesterone replacement therapy on left ventricular systolic and diastolic function parameters in healthy postmenopausal women. METHODS: Forty-six healthy consecutive postmenopausal women were prospectively enrolled. Hormone replacement therapy (HRT), which was either 0.625 mg/day conjugated equine estrogen (CEE) alone, or with 2.5 mg/day medroxyprogesterone acetate (MPA) was administered depending on the hysterectomy status. Left ventricular systolic and diastolic function parameters were evaluated with echocardiography before and after 6 months of HRT. The paired t-test was used for statistical analysis. RESULTS: Estrogen or estrogen plus progesterone did not significantly alter the left ventricular dimensions and systolic function parameters. However, significant improvements were noted in several diastolic function parameters including late diastolic mitral flow velocity, ratio of early to late mitral flow velocity and isovolumic relaxation time (P=0.003, P=0.001 and P=0.005, respectively, for the CEE group; all P<0.001 for the CEE+MPA group). CONCLUSIONS: Estrogen or estrogen plus progesterone replacement therapy may significantly improve left ventricular diastolic functions in healthy postmenopausal women.     

绝经后妇女激素补充治疗后同型半胱氨酸及超声心动图改变的初步观察

目的　观察绝经后妇女激素补充治疗 (HRT)后血浆总同型半胱氨酸 [H(e) ]及超声心动图的改变。方法　将受试者分为 4组。Ⅰ组、Ⅱ组为自然绝经妇女 ,各 30例 ,其中Ⅰ组给予HRT(结合雌激素 0 6 2 5mg d ,安宫黄体酮 2mg d ,或者每月后 14d加安宫黄体酮 4mg d) 3个月 ;Ⅱ组不给予HRT ,为对照 ;Ⅲ组 2 0例 ,为已接受HRT1 5年的绝经后妇女 ;Ⅳ组 2 0例 ,为从未应用HRT的绝经后妇女。Ⅰ组、Ⅱ组受试者于接受HRT前及接受HRT 3个月后测定H(e) ;Ⅲ组、Ⅳ组受试者测定H(e) ,并行超声心动图检查。结果　Ⅰ组、Ⅱ组接受HRT 3个月前后H(e)无明显变化 ,Ⅰ组接受HRT前为(9 3± 2 5 ) μmol L ,Ⅱ组为 (9 4± 2 9) μmol L ;Ⅰ组接受HRT后H(e)为 (9 1± 2 8) μmol L ,Ⅱ组为(9 8± 3 6 ) μmol L。两组比较 ,差异无显著性 (P >0 0 5 )。Ⅲ组H(e)明显低于Ⅳ组 ,分别为 (8 0±1 3) μmol L及 (10 3± 3 2 ) μmol L。两组比较 ,差异有显著性 (P <0 0 5 )。Ⅲ组、Ⅳ组的超声心动图检查结果无明显改变。结论　短期应用HRT对H(e)无明显改善 ,长期应用HRT可降低H(e)水平。绝经后妇女应用HRT 1 5年 ,未见超声心动图有明显变化。     

The effect of hormone replacement therapy on the levels of serum lipids, apolipoprotein AI, apolipoprotein B and lipoprotein (a) in Turkish postmenopausal women

Objectives Estrogen replacement therapy alters the lipid profiles favorably for delaying atherosclerosis in postmenopausal women. The effects of estrogen plus progesterone combination therapy on lipids are controversial. This study was designed to evaluate the effect of female sex hormones on lipids and lipoproteins and to clarify the influence of progesterone on the effect of estrogen in postmenopausal women.Methods Of the 60 postmenopausal women admitted to our menopause clinic, 40 had intact uterus and received continuous 0.625 mg conjugated equine estrogen (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA), whereas the remaining 20 were hysterectomized and received 0.625 mg CEE daily. To assess the alterations in lipids and lipoproteins during menopause, 45 healthy premenopausal women were investigated. Lipid and lipoprotein levels were assessed in each subject at baseline and at the 6th and 18th months of therapy.Results In menopause, a shift towards more atherogenic lipid and lipoprotein profiles than those of the premenopausal state was found. Following 18 months of treatment, both regimens reduced total cholesterol (TC) levels as compared with the baseline (6.4 vs. 6.9% in the CEE/MPA and CEE groups, respectively). The CEE group had a more pronounced increase in high-density lipoprotein (HDL) cholesterol than the CEE/MPA group (10.3 vs. 8.8%, respectively). Both groups displayed reduced TC, low-density lipoprotein (LDL) cholesterol and apolipoprotein-B (ApoB) concentrations, whereas triglycerides increased, with a greater tendency to increase in the CEE/MPA group at the end of the trial. Also, the lipoprotein (a) [Lp(a)] levels decreased significantly (27.6 vs. 24.5% in the CEE/MPA and CEE groups, respectively). This decrease was more pronounced in subjects with a relatively higher basal Lp(a) concentration.Conclusion Both treatment regimens caused positive alterations in the lipid and lipoprotein profiles. This association might play a pivotal role in the postmenopausal increases in atherosclerotic diseases and cardioprotective effect of estrogen in postmenopausal women.     

Effect of hormone replacement therapy, tibolone and raloxifene on serum lipids, apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women.

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxffene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, dimacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n = 34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n = 80), continuous combined 17beta-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n = 58), tibolone 2.5 mg (n = 83) and raloxifene HCl 60 mg (n = 50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (-11.2%, -11.9% and -11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA1 were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA1, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, -13.6%; and ApoA1, -9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (-13.2 to -29.0%). In conclusion, each therapy regimen had a diferent effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

Effect of hormone replacement therapy,tibolone and raloxifene on serum lipids,apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxifene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, climacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n=34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n=80), continuous combined 17β-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n=58), tibolone 2.5 mg (n=83) and raloxifene HCl 60 mg (n=50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA₁), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (?11.2%, ?11.9% and ?11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA₁ were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA₁, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, ?13.6%; and ApoA₁, ?9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (?13.2 to ?29.0%). In conclusion, each therapy regimen had a different effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

Short-term effects of hormone therapy on serum C-reactive protein levels in postmenopausal women

Objectives: The aim of this study was to investigate the effects of tibolone and conjugated equine estrogens (CEEs) plus medroxyprogesterone acetate (MPA) (CEE + MPA) on levels of serum C-reactive protein (CRP), an independent risk factor for cardiovascular disorders, in postmenopausal women. Study design: In this prospective randomized study, we randomly assigned 58 healthy postmenopausal women to CEE (0.625 mg/day) plus MPA (2.5 mg/day) (CEE + MPA) or tibolone (2.5 mg/day). The serum levels of CRP at 3 months after starting treatment were compared with baseline values for both therapies. Results: After 3 months of treatment the median CRP levels increased by 29% in the CEE + MPA group and by 5% in the tibolone group. But, these changes did not have statistical significance (P=0.15, P=0.06, respectively). Conclusions: Our findings show that neither tibolone nor CEE + MPA caused significant changes in serum CRP levels in postmenopausal women. The potential impact of hormone therapy on serum CRP levels should be investigated in ongoing clinical trials.     

Effect of conjugated equine estrogen in combination with two different progestogens on the risk factors of coronary heart disease in postmenopausal Chinese women in Taiwan: a randomized one-year study

BACKGROUND: To compare the effect of hormone replacement therapy (HRT) using estrogen plus dydrogesterone or estrogen plus medroxyprogesterone acetate (MPA) on the risk factors for coronary heart disease (CHD) in postmenopausal women. METHODS: A randomized, prospective 1-year clinical trial was designed. All of the postmenopausal women (n = 279) received sequential conjugated equine estrogen (CEE) at a dose of 0.625 mg/day for 25 days (days 1-25) of each month. These women were also randomly assigned to receive either dydrogesterone 10 mg/day (E + D group, n = 140) or MPA 5 mg/day (E + P group, n = 139) for 14 days (days 12-25) of each month. Serum biochemical markers, lipoproteins, plasma prothrombin time (PT), partial prothrombin time (PPT) and antithrombin III-antigen (ATIII-Ag) were analyzed at baseline, and after 6 and 12 months of treatment. RESULTS: Liver function, renal function, PT and PPT did not change significantly during the 12-month trial. The E + D group had a more pronounced increase in high density lipoprotein cholesterol (HDL-C) than the E + P group (10.6% vs. 2.7%) after 12 months of treatment (p < 0.05). Both groups showed reduced concentrations of total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C) and ATIII, whereas triglyceride (TG) was increased at the end of the trial (without intergroup difference). CONCLUSIONS: Our study demonstrated a favorable effect on lipoprotein profiles with both hormone replacement therapy regimens. Dydrogesterone appears to be superior to medroxyprogesterone acetate from the perspective of modification of coronary heart disease risk factors.     

Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate.

OBJECTIVE: To determine the endometrial safety of lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA). DESIGN: Randomized, double-blind, placebo-controlled study (the Women's Health, Osteoporosis, Progestin, Estrogen study). SETTING: Study centers across the United States. PATIENT(S): Healthy, postmenopausal women (n = 2,673) with an intact uterus. INTERVENTION(S): Patients received CEE 0.625 mg/day, CEE 0.625/MPA 2.5 mg/day, CEE 0.45 mg/day, CEE 0.45/MPA 2.5 mg/day, CEE 0.45/MPA 1.5 mg/day, CEE 0.3 mg/day, CEE 0.3/MPA 1.5 mg/day, or placebo for 1 year. Endometrial biopsies were evaluated at baseline, cycle 6, and year 1 using a centralized protocol.MAIN OUTCOME MEASURE(S): Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed CEE. RESULT(S): Endometrial hyperplasia rates ranged from 0 to 0.37% for all CEE/MPA doses. Twenty-nine of the 32 cases of endometrial hyperplasia developed in women who were administered CEE 0.625 mg or CEE 0.45 mg. The incidence of endometrial hyperplasia increased with age for patients administered CEE alone. As expected, there were some inconsistencies among pathologists' ratings in the numbers of hyperplasias and incidence rates for the CEE-alone regimens. There were too few cases of hyperplasia in the combination groups to evaluate consistency among pathologists. CONCLUSION(S): One year of treatment with lower doses of CEE/MPA provides endometrial protection comparable to commonly prescribed doses. These regimens may be used by clinicians to individualize hormone replacement therapy in postmenopausal women.     

Hormone substitution therapy. Side-effects and compliance of various therapeutic regimens]

BACKGROUND: The aim of this study is to evaluate the tolerability and long-term compliance of four Estrogen Progestin treatments (HRT) for menopause. METHODS: One hundred and ten symptomatic menopausal women were divided into four groups according to therapeutic regimens: A) Estradiol (E2) transdermal treatment 50 micrograms (TTS 50) continuously administered (cont.) plus Medroxyprogesterone Acetate (MPA) 10 mg/die for twelve days a month: 35 women. B) Conjugated Equine Estrogens (CEE) 0.625 mg/die cont. plus MPA for twelve days a month: 25 women. C) Estradiol transdermal 50 micrograms (cont.) plus MPA 2.5 mg/die cont.: 26 women. D) CEE 0.625 mg/die cont. plus MPA 2.5 mg/die cont.: 24 women. RESULTS: Menopausal symptoms were significantly reduced with all treatments. During the first year group C and D patients showed irregular bleeding (group C: 46%, group D: 61%). After 24 months the bleeding frequency was reduced (group C: 11%, group D: 13%). Mastodynia was the more frequent side-effect in particular among women who were utilizing cont.comb. regimens. The total percentage of drop out (D.O.) after 2 years was more than 30% (Group A: 31%, Group B: 33%, Group C: 39%, Group D: 35%). The most frequent reasons for abandoning HRT (79% of all DO) were not linked to therapy side-effects. 19% of DO switched to other hormonal regimens.     

Psychological effects of tibolone and sequential estrogen-progestogen therapy in perimenopausal women.

OBJECTIVE: To investigate changes in psychological symptoms before and after continuous tibolone treatment and sequential estrogen-progestogen therapy in perimenopausal women. METHODS: In this prospective, randomized, controlled study, perimenopausal women were randomly allocated to treatment with either tibolone 2.5 mg/day for 28 days (n = 28), or 0.625 mg conjugated equine estrogens (CEE) for 25 days plus 5 mg medroxyprogesterone acetate (MPA) daily on days 16-25 (n = 33). The differences in Beck's depression scores and serum lipid profiles before and after 1 year of treatment with both regimens were compared. RESULTS: Both groups were similar with respect to demographic characteristics. The differences in Beck's depression scores before and after treatment were statistically significant in the tibolone group (21.3 vs 17.1, p = 0.038) and also in the group receiving standard sequential estrogen-progestogen treatment (15.7 vs. 13.0, p = 0.040). In the sequential estrogen-progesterone group, a statistically significant increase was measured in high-density lipoprotein (HDL)-cholesterol levels after treatment (49.1 vs. 56.8 mg/dl, p = 0.023). CONCLUSION: Tibolone is as effective as sequential estrogen-progesterone therapy in alleviating the psychological symptoms of the perimenopause. In addition, CEE + MPA induces favorable changes in HDL-cholesterol.     

Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women.

OBJECTIVE: To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm. METHODS: Sixty postmenopausal women in a stable relationship with a partner capable of intercourse, and presenting sexual complaints that appeared after menopause, were randomly divided into two groups: EP (n = 29) received one tablet of equine estrogens (CEE) 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg and one capsule of placebo; EP + A (n = 31) received one tablet of CEE 0.625 mg plus MPA 2.5 mg and one capsule of methyltestosterone 2.0 mg; The treatment period was 12 months. The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale. The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency. RESULTS: There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment (p = 0.021). No significant effect on orgasmic capacity was noted after the treatment period. CONCLUSION: Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy, but might not affect the ability to obtain orgasm in sexual relations.     

Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding

Objective: To evaluate vaginal bleeding profiles with lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as continuous combined therapy.

Design: The Women’s Health, Osteoporosis, Progestin, Estrogen (Women’s HOPE) study, a randomized, double-blind, placebo-controlled trial.

Setting: Study centers across the United States.

Patient(s): Two thousand six hundred seventy-three healthy, postmenopausal women.

Intervention(s): Women received CEE, 0.625 mg/d; CEE, 0.625 mg/d, plus MPA 2.5 mg/d; CEE, 0.45 mg/d; CEE, 0.45 mg/d, plus MPA, 2.5 mg/d; CEE 0.45 mg/d, plus MPA, 1.5 mg/d; CEE, 0.3 mg/d; CEE, 0.3 mg/d, plus MPA, 1.5 mg/d; or placebo for 1 year.

Main Outcome Measure(s): Bleeding data were analyzed in efficacy-evaluable and intention-to-treat populations.

Result(s): Cumulative amenorrhea and no bleeding rates were higher with lower doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between time since menopause and cumulative amenorrhea was observed (P<.05) in all CEE/MPA groups except the CEE 0.45/MPA 1.5 group. The proportion of patients who experienced no bleeding in cycle 1 was 89%, 82%, and 80% in the CEE 0.3/MPA 1.5, CEE 0.45/MPA 1.5, and CEE 0.45/MPA 2.5 groups, respectively. These values were significantly greater than the incidence of no bleeding in the CEE 0.625/MPA 2.5 group (P<.05).

Conclusion(s): Lower-dose regimens of CEE and MPA produce higher rates of amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be appropriate for newly menopausal patients.     

Effect of hormone replacement therapy and tibolone on serum total homocysteine levels in postmenopausal women

OBJECTIVE: To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. STUDY DESIGN: Ninety-five postmenopausal women aged 41-68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31) or tibolone 2.5 mg (n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. RESULTS: No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: -15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: -3.23%, NS). CONCLUSION: Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results.     

Effect of steroid add-back therapy on the proliferative activity of uterine leiomyoma cells under gonadotropin-releasing hormone agonist therapy

Short-term treatment with gonadotropin-releasing hormone agonist (GnRHa) is a useful preoperative medical therapy of uterine leiomyomas. However, adverse effects caused by the hypo-estrogen state sometimes appear, suggesting the necessity of add-back therapy. In this study, we investigated effects of three kinds of add-back therapies on the proliferative activity of uterine leiomyoma cells by examining the expression of Ki-67 in leiomyoma cells by immunostaining. Thirty patients who were to undergo hysterectomy or myomectomy were injected with 3.75?mg depot leuprolide acetate every four weeks until the end of the 12th week. Twenty patients underwent add-back therapy from the 5th week to the end of the 12th week, 8 patients receiving 0.625?mg of conjugated equine estrogen (CEE) /day, 6 patients 5.0?mg of medroxyprogesterone acetate (MPA)/day, 6 patients 0.625?mg CEE plus 2.5?mg of MPA /day. The add-back of CEE or CEE plus MPA suppressed decreases in the proliferative activity of leiomyoma cells caused by GnRHa therapy, but that of MPA did not. These results suggest that the add-back therapy with MPA is of use in preventing the adverse effects caused by hypo-estrogen in the preoperative short-term GnRHa therapy.     

The comparison of bleeding patterns with high-dose and low-dose hormone replacement therapy in postmenopausal women.

Our objective was to compare vaginal bleeding patterns with lower doses of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), in a randomized, double-blind, placebo-controlled trial. A total of 112 healthy, postmenopausal women were divided into three groups. Group A received CEE 0.625 mg/day plus MPA 2.5 mg/day; group B received CEE 0.3 mg/day, plus MPA 1.25 mg/day; and another group received placebo. All medications were continued for 13 months and bleeding data were analyzed in each group. The percentage of patients who experienced no bleeding in cycle one was 45.2% in group B. These values were significantly greater than the figure for group A (18.2%) and lower than in the placebo group (66.7%). A linear trend between time since menopause and cumulative amenorrhea was observed in cases in group B and the placebo group in all cycles (p < 0.05). This finding was significant in only cycle 13 in group A. In conclusion, a higher rate of amenorrhea was observed with a lower-dose regimen of CEE/MPA, which may be the appropriate regimen.     

Effect of steroid add-back therapy on the proliferative activity of uterine leiomyoma cells under gonadotropin-releasing hormone agonist therapy.

Short-term treatment with gonadotropin-releasing hormone agonist (GnRHa) is a useful preoperative medical therapy of uterine leiomyomas. However, adverse effects caused by the hypo-estrogen state sometimes appear, suggesting the necessity of add-back therapy. In this study, we investigated effects of three kinds of add-back therapies on the proliferative activity of uterine leiomyoma cells by examining the expression of Ki-67 in leiomyoma cells by immunostaining. Thirty patients who were to undergo hysterectomy or myomectomy were injected with 3.75 mg depot leuprolide acetate every four weeks until the end of the 12th week. Twenty patients underwent add-back therapy from the 5th week to the end of the 12th week, 8 patients receiving 0.625 mg of conjugated equine estrogen (CEE) /day, 6 patients 5.0 mg of medroxyprogesterone acetate (MPA)/day, 6 patients 0.625 mg CEE plus 2.5 mg of MPA /day. The add-back of CEE or CEE plus MPA suppressed decreases in the proliferative activity of leiomyoma cells caused by GnRHa therapy, but that of MPA did not. These results suggest that the add-back therapy with MPA is of use in preventing the adverse effects caused by hypo-estrogen in the preoperative short-term GnRHa therapy.     

Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate

Objective: To evaluate the efficacy of lower doses of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for relieving vasomotor symptoms and vaginal atrophy.

Design: A randomized, double-blind, placebo-controlled trial (the Women’s Health, Osteoporosis, Progestin, Estrogen study).

Setting: Study centers across the United States.

Patient(s): Two thousand, six hundred, seventy-three healthy, postmenopausal women with an intact uterus, including an efficacy-evaluable population (n = 241 at baseline).

Intervention(s): Patients received for 1 year (13 cycles; in milligrams per day) CEE, 0.625; CEE, 0.625 and MPA, 2.5; CEE, 0.45; CEE, 0.45 and MPA, 2.5; CEE, 0.45 and MPA, 1.5; CEE, 0.3; CEE, 0.3 and MPA, 1.5; or placebo.

Main Outcome Measure(s): Number and severity of hot flushes and Papanicolaou smear with vaginal maturation index (VMI) to assess vaginal atrophy.

Result(s): In the efficacy-evaluable population, reduction in vasomotor symptoms was similar with CEE of 0.625 mg/d and MPA of 2.5 mg/d (the most commonly prescribed doses) and all lower combination doses. CEE of 0.625 mg/d alleviated hot flushes more effectively than the lower doses of CEE alone. VMI improved in all active treatment groups.

Conclusion(s): Lower doses of CEE plus MPA relieve vasomotor symptoms and vaginal atrophy as effectively as commonly prescribed doses.     

Efficacy of every-other-day administration of conjugated equine estrogen and medroxyprogesterone acetate on gonadotropin-releasing hormone agonists treatment in women with endometriosis.

We performed a randomized controlled study to determine the efficacy of add-backed therapy by every-other-day administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) on GnRH agonists (GnRH-a) treatment in Japanese women with symptomatic endometriosis. At the end of treatment, serum estrone and estradiol levels in the add-back group (n = 11) were significantly higher than those in the control group (n = 10). The assessment of Beecham classification by bimanual examination, serum CA-125 levels, and the frequency of genital bleeding revealed no significant differences between the two groups. The add-back group showed reduced Kupperman indices relative to those of the control group, and could prevent the loss of bone density. These findings led to a conclusion that GnRH-a therapy added back by every-other-day administration of 0.625 mg CEE and 2.5 mg MPA was a safe and effective treatment for Japanese women with endometriosis.     

The comparison of bleeding patterns with high-dose and low-dose hormone replacement therapy in postmenopausal women

Our objective was to compare vaginal bleeding patterns with lower doses of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), in a randomized, double- blind, placebo-controlled trial. A total of 112 healthy, postmenopausal women were divided into three groups. Group A received CEE 0.625 mg/day plus MPA 2.5 mg/day; group B received CEE 0.3 mg/day, plus MPA 1.25 mg/day; and another group received placebo. All medications were continued for 13 months and bleeding data were analyzed in each group. The percentage of patients who experienced no bleeding in cycle one was 45.2% in group B. These values were significantly greater than the figure for group A (18.2%) and lower than in the placebo group (66.7%). A linear trend between time since menopause and cumulative amenorrhea was observed in cases in group B and the placebo group in all cycles (p <?0.05). This finding was significant in only cycle 13 in group A. In conclusion, a higher rate of amenorrhea was observed with a lower-dose regimen of CEE/MPA, which may be the appropriate regimen.     

The effect of the phytoestrogen genistein and hormone replacement therapy on homocysteine and C-reactive protein level in postmenopausal women

BACKGROUND: The aim of the study was to evaluate the effect, in postmenopausal women, of the phytoestrogen genistein and hormone replacement therapy (HRT) on circulating two independent factors of cardiovascular risk: homocysteine and C-reactive protein (CRP). METHODS: Ninety healthy postmenopausal women, from 50 to 60 years of age, were randomly assigned to receive genistein (n = 30; 54 mg/die) or continuous combined estrogen/progestin therapy (17-beta-estradiol 1 mg plus norethisterone acetate 0.5 mg) or placebo. Plasma homocysteine and serum CRP were measured at baseline and after 6 months of treatment. RESULTS: In the genistein group, plasma homocysteine and serum CRP showed no statistically significant difference from baseline (homocysteine: 11.36 +/- 0.39 micromol/l; CRP: 1.73 +/- 0.31 mg/l) to 6 months treatment (homocysteine: 10.72 +/- 0.46 micromol/l; CRP: 2.13 +/- 0.45 mg/l), without any significant difference versus the placebo group (homocysteine: 11.25 +/- 0.43 micromol/l; CRP: 1.74 +/- 0.22 mg/l). In the HRT group there was a slight, but not significant reduction, of plasma homocysteine mean value from baseline (11.21 +/- 0.44 micromol/l) to 6 months treatment (10.45 +/- 0.38 micromol/l); whereas CRP mean value at the end of treatment (3.30 +/- 0.55 mg/l) was significantly higher from baseline (1.61 +/- 0.25 mg/l) (P < 0.01). However, after 6 months, no significant difference existed with the other two groups. CONCLUSIONS: The phytoestrogen genistein, after 6 months treatment, does not modify the independent cardiovascular risk linked to circulating homocysteine or CRP level. Our experience confirms critical increase of CRP serum level after HRT treatment, but not plasma homocysteine significant variation.