The effect of hormone replacement therapy on postmenopausal bone loss.

Eighty-four postmenopausal women who were randomly allocated to one of four groups, completed a 1 year follow-up. The first group (n = 20) received 0.625 mg/day conjugated estrogens cyclically (CE; 25 days/month). The second (n = 23) received 0.625 mg/day of CE continuously, and the third (n = 17) received 50 micrograms/day of transdermal 17 beta-estradiol cyclically (24 days/month). All these groups also received 2.5 mg of medroxiprogesterone acetate sequentially for the last 12 days of hormone replacement therapy, while the fourth group (n = 24) constituted a treatment-free control group. Dual photon absorptiometry was carried out before therapy and was repeated after 1 year. Serum calcium, phosphate and osteocalcine levels, and the urinary calcium/creatinine and hydroxyproline/creatinine ratios, were measured prior to treatment and 6 and 12 months thereafter. All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous CE treatment group (4.4%, P less than 0.05) and in transdermal group (7.1%, P less than 0.01). Concomitant biochemical effects at 6 and 12 months, reduction in urine calcium and hydroxyproline, reduction in blood calcium, phosphate and osteocalcine, were compatible with the observed effects on bone mineral.     

绝经后激素治疗适应证

伴随绝经过程及绝经后内分泌事件对妇女健康产生的不良影响,出现了一些临床问题需要激素治疗来纠正。激素治疗纠正这些健康问题是效价比最佳的措施。目前激素治疗主要有三大适应证:缓解绝经相关症状、治疗泌尿生殖道萎缩相关疾病、预防和治疗骨质疏松症。     

Effect of hormone replacement therapy and calcitonin on bone mass in postmenopausal women.

A total of 104 postmenopausal women were randomly assigned to different therapeutic regimens: (a) calcitonin, (b) estrogen/progestogen (HRT) plus calcitonin, (c) estrogen/progestogen (HRT), (d) and the control group. The bone mass of the lumbar vertebrae of all patients was assessed with a dual beam photon absorptiometer (Norland GD 153). The 73 patients who completed the 1-yr study showed that postmenopausal bone loss could be prevented by either estrogen/progestogen (HRT) or calcitonin. In addition, the combination of hormonal replacement therapy and calcitonin not only prevented post-menopausal bone loss but resulted in a significant 10% gain in bone mass (P < 0.001).     

Transdermal hormone replacement therapy in postmenopausal women with uterine leiomyomas.

OBJECTIVE: To evaluate the effects of transdermal hormone replacement therapy (HRT) on uterine and leiomyoma size and on uterine bleeding patterns in postmenopausal women with uterine leiomyomas. METHODS: The required sample size was calculated to be 30 subjects per group to detect an effect on the size of one standard deviation (SD) with an alpha value of 0.05 (two-sided) and a power 1 - delta = 0.8. At the end of the study, the power analysis showed a value of beta = 0.826. Seventy postmenopausal women with uterine leiomyomas were enrolled and treated for 12 cycles of 28 days each with transdermal 17 beta-estradiol (E(2)) patches plus oral medroxyprogesterone acetate continuously added (group A) or with calcium carbonate (group B). At entry and every three cycles, uterine and leiomyoma dimensions were measured by transvaginal ultrasonography. To evaluate the effect of transdermal HRT on the characteristics of uterine bleeding, 35 healthy postmenopausal women without uterine leiomyomas (group C) were enrolled and treated with the same regimen as group A. A daily diary was used to record the abnormal uterine bleeding episodes, and a rank scale was used to assess the severity of bleeding. RESULTS: There were no significant changes in mean uterine or leiomyoma size between groups A and B, or in each group compared with basal values. No significant difference was detected between groups A and C in uterine bleeding patterns. CONCLUSION: Transdermal HRT did not increase the size of uterine leiomyomas or affect uterine bleeding patterns in postmenopausal women.     

Sex hormone binding globulin capacity and postmenopausal hormone replacement therapy.

The sex hormone binding globulin (SHBG) capacity was measured in 26 normal untreated postmenopausal women and 10 postmenopausal women taking different types of hormone replacement therapy. The patients on hormone replacement therapy had significantly higher levels of SHBG than postmenopausal women (p less than 0.001) and also significantly higher levels than 52 normal ovulating women studied previously (Pogmore and Jequier, 1979; p less than 0.02). This suggests that postmenopausal women on hormone therapy are being overtreated.     

Compliance with hormone replacement therapy in postmenopausal Sicilian women

OBJECTIVE: To verify the compliance with hormone replacement therapy (HRT) over 2 years in a population of postmenopausal women in East Sicily. STUDY DESIGN: Patients starting hormonal therapy for the first time were enrolled in this study. A telephone survey was then conducted after 3, 6, 12 and 24 months and the reasons for any discontinuation were recorded. RESULTS: Of a total of 138 women who agreed to be enrolled in this prospective longitudinal study 72 were still taking the treatment after 1 year and only 56 at the end of the study, although only three patients reported that they had experienced no benefit. CONCLUSIONS: Type of work, surgical menopause and previous use of oral contraceptives were significantly statistically associated with better HRT compliance. Side effects and fear of breast cancer, which we maintain is exaggerated by the women and their family doctors, were the commonest reasons for early discontinuation of the hormonal treatment.     

Combination of statins and hormone replacement therapy in postmenopausal women is associated with increased bone mineral density.

Recent studies have shown that statins might be potent inhibitors of bone resorption and osteoclast number, and there is evidence for their bone anabolic effects. Statin treatment seems to protect against non-pathological fractures in older women. However, contradictory findings have been obtained. In this retrospective study we found that postmenopausal women on statins and hormone replacement therapy (HRT) showed higher bone mineral density than women on HRT alone. This evidence provides further confirmation of the effect of statins on bone turnover and shows that the combination of HRT and statins reduces the risk of bone fracture by virtue of the antiresorptive effect of HRT and the anabolic and antiresorptive effects of statins.     

An objective and subjective assessment of uterine blood loss in postmenopausal women on hormone replacement therapy.

OBJECTIVE: To determine the volume of withdrawal blood loss in women taking hormone replacement therapy (HRT). DESIGN: Prospective randomized double blind cross-over trial. SUBJECTS: Twenty-nine postmenopausal women, with climacteric symptoms. INTERVENTIONS: The women were treated with cycles of 2 mg oestradiol valerate for 21 days combined with either 250 micrograms levonorgestrel or 10 mg medroxyprogesterone acetate, for the last ten days. Each woman was randomly allocated to one of the preparations and switched to the other after four months. MAIN OUTCOME MEASURES: Uterine blood loss was estimated by the alkaline haematin method. Bleeding patterns were recorded specifying the number of days with bleeding and subjective rating of the amount of blood lost. RESULTS AND CONCLUSIONS: The mean uterine blood loss was 35.2 ml and was equivalent to the normal menstrual blood loss. There was no significant difference between therapies but the women themselves considered that they bled more heavily when taking the levonorgestrel combination. The intraindividual variation in blood loss was small, independent of preparation taken, but the variation between individuals was large. Withdrawal bleeding started 2-3 days earlier when the women used the medroxyprogesterone acetate compared to the levonorgestrel formulation.     

Decrease of serum endothelin levels with postmenopausal hormone replacement therapy or tibolone.

Endothelin is the most potent vasoconstrictor peptide known to date. Hormone replacement therapy (HRT) with estrogen reduces plasma endothelin levels. We measured endothelin in 51 postmenopausal patients before and during HRT. Patients were randomly allocated to receive either oral tibolone, oral or transdermal 17 beta-estradiol. A group of comparable volunteers served as controls. After 24 months, endothelin levels decreased in all treatment groups: tibolone, 18.2%; oral 23.1%; transdermal, 20.8%. Endothelin levels increased in the controls by 36.6% (p < 0.01). Tibolone decreases endothelin levels to a similar degree as conventional estrogen-progestogen-replacement therapy. These data provide another potential mechanism supporting the cardioprotective effects of tibolone.     

Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women.

In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms, two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 microg/day and progesterone 20 mg/day, while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone, estradiol and progesterone were measured at pretreatment, weekly for 4 weeks, and then monthly for 4 months. The incidence of hot flushes, frequency of night sweats, mood scores, vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring, the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment, owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring, although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.     

Effects of postmenopausal hormone replacement therapy on body fat composition.

AIM: To evaluate the effects of different types, regimens and administration routes of hormone replacement therapy (HRT) on body fat composition indices in postmenopausal women at increased risk of anthropometry-related cardiovascular disease (CVD). METHODS: Fifty-nine postmenopausal women (aged 41-57 years, mean +/- standard deviation: 49.9 +/- 3.8 years) with body mass index (BMI) > or =25 kg/m(2) participated in this 6-month, prospective, randomized single-blind study. Subjects were assigned into three groups and received transdermal estradiol (E2)/norethisterone acetate (NETA) (50 microg E2 daily for 14 days followed by 50 microg E2/0.25 microg NETA daily for 14 days; transdermal group, n = 19), transdermal continuous E2/oral medroxyprogesterone acetate (MPA) (50 microg E2/5 mg MPA daily; transdermal/oral group, n = 19) or oral continuous E2/NETA (1 mg E2/0.5 mg NETA daily; oral group, n = 21). Anthropometric indices (body weight, height, and hip and waist circumferences) were measured, and BMI and waist-to-hip ratio (WHR) were calculated, before and after treatment. Also, the thickness of subcutaneous abdominal fat was measured by ultrasound. Depending on waist circumference (WC), the subjects were divided into two risk groups: increased-risk group with WC <88 cm (n = 32) and high-risk group with WC > or =88 cm (n = 27). Also, the effects of HRT were evaluated separately in subjects with median subcutaneous fat of <33 mm (n = 29) and those with median subcutaneous fat of > or =33 mm (n = 30). RESULTS: Overall, all three types of HRT caused a significant decrease in both WC and subcutaneous fat (p < 0.001), and also in WHR (p < 0.05). There was no significant difference in baseline (p > 0.05) and final values (p > 0.05) between HRT groups. In each group, all types of HRT significantly decreased WC and subcutaneous fat (transdermal group: p < 0.001 and p < 0.05; transdermal/oral group: p < 0.001 and p < 0.01; oral group: p < 0.001 and p < 0.001, respectively), while body weight, BMI and WHR changed only insignificantly (p > 0.05). In the increased-risk group, body weight increased significantly (p < 0.05) while WC and subcutaneous fat decreased significantly (p < 0.001 and p < 0.001). As for the high-risk group, there was a significant decrease in WC and subcutaneous fat (p < 0.001, p < 0.001) while the remaining parameters did not change significantly. However, BMI showed a tendency to increase in the increased-risk group, while there was a decrease in all measurements in the high-risk group. Regardless of the drugs used and baseline subcutaneous fat, WC and subcutaneous fat decreased significantly at the end of the treatment (subcutaneous fat <33 mm: p < 0.001 and p < 0.01; subcutaneous fat > or =33 mm: p < 0.001 and p < 0.001, respectively). CONCLUSIONS: The three different types of HRT have comparable effects on central fat tissue in women at increased risk of anthropometry-related CVD. Indeed, the three combinations of HRT reduced fat tissue in the central part of the body. However, the overall effect of HRT was more marked in women with WC > or =88 cm and subcutaneous fat > or =33 cm. Whether HRT increases body weight depends on the body composition indices of individuals before treatment.     

Long-term postmenopausal hormone replacement therapy effects on bone mass: differences between surgical and spontaneous patients.

BACKGROUND: Hormone Replacement Therapy (HRT) begun soon after spontaneous menopause or oophorectomy minimizes or even reverses the loss of bone that occurs normally during those years. The persistence of this HRT protective effect at long-term on bone density, however, is not well documented. AIM: to evaluate the effects of 5 years of HRT in postmenopausal women on bone mineral density of the lumbar spine. SUBJECTS AND METHODS: The 5-year prospective study enrolled 154 postmenopausal women, of them 136 completed the first year and were considered electible to continue the follow-up. These 136 postmenopausal women were allocated to two groups according their origin: surgical (n=68) and spontaneous (n=68). HRT was prescribed and bone mineral density (BMD) was measured at the lumbar spine prior to commencement of therapy, and then yearly for the duration of the study. All patients received a continuous therapy with standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or 50 microg/day of 17-beta-Estradiol in transdermal therapeutic systems (TTS). Subjects who experienced natural menopause also received 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Treated groups were compared with two non-treated control groups (surgical n=77; spontaneous n=53). RESULTS: Our data showed that HRT increased the BMD of women who had experienced spontaneous menopause. Comparison with a control group revealed that HRT also protected against bone loss in women who had undergone surgical menopause. CONCLUSION: Long term hormone replacement therapy increases bone mineral density in women who have experienced natural menopause, and protects against bone loss in surgically postmenopausal women.     

Combination of statins and hormone replacement therapy in postmenopausal women is associated with increased bone mineral density

Recent studies have shown that statins might be potent inhibitors of bone resorption and osteoclast number ,and there is evidence for their bone anabolic effects. Statin treatment seems to protect against non-pathological fractures in older women. However ,contradictory findings have been obtained. In this retrospective study we found that postmenopausal women on statins and hormone replacement therapy (HRT) showed higher bone mineral density than women on HRT alone. This evidence provides further confirmation of the effect of statins on bone turnover and shows that the combination of HRT and statins reduces the risk of bone fracture by virtue of the antiresorptive effect of HRT and the anabolic and antiresorptive effects of statins.     

A comparison of circulating hormone levels in postmenopausal women receiving hormone replacement therapy.

Seventeen postmenopausal subjects were randomized into this comparative study of esterified estrogen 0.625 mg (Estratab), esterified estrogen 0.625 mg plus 1.25 mg methyltestosterone (Estratest H.S.), or conjugated estrogen 0.625 mg (Premarin). Sixteen subjects completed the study in which plasma hormone concentrations of estrone and estradiol were assessed at various time points. There were no significant differences among the treatment groups.     

Effects of smoking on serum lipoproteins and bone mineral content during postmenopausal hormone replacement therapy

We examined the effect of smoking on the treatment response in serum estrogens, serum lipids and lipoproteins, and bone mineral content in 110 postmenopausal women treated for 2 years with either percutaneous or orally administered combined hormones or placebo and followed up by examinations every 3 months. Serum estradiol and estrone levels during oral hormone administration were lower in smokers than in nonsmokers, whereas no differences related to smoking habits were observed during percutaneous hormone administration. Serum total and low-density lipoprotein cholesterol were significantly reduced in both smokers and nonsmokers receiving hormones, but the response in smokers was only half that observed in nonsmokers (not significant). When the impact of the route of hormone administration was examined in relation to smoking habits, the response in serum total and low-density lipoprotein cholesterol in smokers receiving oral hormones was significantly lower (p less than 0.05) than that observed in nonsmokers. No differences in serum lipids or lipoproteins were observed between smokers and nonsmokers receiving percutaneous hormones. The response in bone mineral content in smokers and nonsmokers receiving percutaneous hormones and placebo was not significantly different, although the overall response differed significantly in the two groups (p less than 0.001). In contrast, the response in smokers receiving oral hormones was significantly lower than that observed in the corresponding nonsmokers (p less than 0.01). We conclude that smoking greatly affects the response on circulating levels of estrogens in postmenopausal women treated with orally administered hormone replacement therapy and that the subsequent treatment response on serum lipids and lipoproteins and on bone mineral content is reduced accordingly. The study suggests that alternative routes of administration should be considered when postmenopausal estrogen therapy is instituted in women who smoke.     

Effect of hormone replacement therapy on glucose tolerance in postmenopausal women.

Oral glucose tolerance tests were performed on 50 symptomatic postmenopausal women before and after three months of hormone replacement therapy. All patients were randomly allocated to one of five groups treated with various synthetic or so-called naturally occurring oestrogens. Therapy produced a significant deterioration of carbohydrate tolerance with sequential preparations containing 100 microgram of ethinyl oestradiol or graduated doses of mestranol up to 50 microgram. The conjugated equine oestrogen (1.25 mg daily) and oestrogen valerate (2 mg daily) treated groups did not show abnormal glucose tolerance. The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed.