The effects of hormone replacement therapy on plasma lipids in type II diabetes

Objectives: The effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women with non-insulin dependent diabetes mellitus (type II diabetes) is uncertain. Methods: The effects of estrogen replacement therapy (ERT, conjugated equine estrogen 0.625 mg orally daily), combined estrogen and continuous progestogen therapy (HRT, 0.625 mg of conjugated equine estrogens plus medroxyprogesterone acetate 5 mg daily) or placebo was compared in 20 postmenopausal type II diabetic women and 20 normal postmenopausal women in a double blind, randomised, crossover study. Patients receiving insulin were excluded from the study and all lipid modifying drugs were ceased at least 4 weeks prior to randomisation. Other medication including oral hypoglycaemics was kept constant for the duration of the study. Results: Women with type II diabetes were a similar age (58.7±1.3 years) to the non-diabetic women (59.6±1.6 years) but they had a significantly greater body mass index, a higher incidence of treated hypertension, higher fasting plasma glucose levels, higher triglycerides and lower HDL cholesterol levels than non-diabetic women. ERT reduced total cholesterol and LDL cholesterol by a similar extent (8.9–12.3%) in normal and type II diabetic women and increased HDL cholesterol to a similar extent in both groups (11.0 and 8.9% respectively). ERT did not significantly alter fasting triglyceride levels in either group. The addition of medroxyprogesterone acetate 5 mg daily abolished the increase in HDL cholesterol associated with ERT in both groups but did not significantly affect any of the other lipid measurements. ERT and HRT did not significantly alter fasting insulin levels nor alter fasting glucose levels in either non-diabetic women or women with type II diabetes. Conclusions: ERT and HRT have similar effects on lipids in women with type II diabetes and non-diabetic women after 1 month of therapy.     

Hormone replacement therapy and risk for coronary heart disease. Data from the CORA-study--a case-control study on women with incident coronary heart disease

BACKGROUND: Hormone replacement therapy (HRT) has been suggested to prevent cardiovascular disease, while some intervention studies have shed doubt on this concept. Thus, uncertainty remains whether current HRT use is beneficial as to cardiovascular disease or may even be harmful. OBJECTIVES: This research investigates the association of hormone replacement therapy, risk factors and lifestyle characteristics with the manifestation of coronary heart disease in current HRT users versus never users. DESIGN: The coronary risk factors for atherosclerosis in women study (CORA-study) provide clinical and biochemical parameters and data on lifestyle in 200 consecutive pre- and postmenopausal women with incident coronary heart disease compared to 255 age-matched population-based controls, of which 87.9% were postmenopausal. RESULTS: Significantly more controls than cases used currently HRT for a median of 9.5 years (32.9% versus 20.2%), while 50.0% of cases and 42.5% of controls had never used HRT (p<0.02). Compared to women who never used HRT, current users ate less meat and sausage, had a significantly lower BMI and waist-to-hip ratio and a lower prevalence of hypertension, insulin resistance and diabetes. However, current users among cases were often smokers and smoked significantly more cigarettes than never users. In a multivariate analysis the risk of current HRT users for coronary artery disease was 57% lower than the risk of never users (odds ratio 0.428, CI 0.206-0.860, p<0.02). Adjustment for conventional and dietary risk factors revealed neither current HRT use, nor HRT use combined with smoking as independent risk factors. CONCLUSIONS: These data from the CORA-study are not compatible with an adverse impact of hormone replacement therapy on cardiovascular disease, rather support the notion of beneficial effects of HRT on weight, central adiposity, insulin sensitivity and blood pressure. Yet, the data do not support the presumption of a general healthy user effect in women on HRT either. Rather, in some women adverse lifestyle habits, especially intense smoking, appear to counteract possible beneficial effects of HRT.     

Hormone replacement therapy improves arterial stiffness in normotensive postmenopausal women

Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks.     

Hormone replacement therapy: the perspectives for the 21st century.

Nowadays different lines of evidence demonstrate the benefits of postmenopausal hormone replacement therapy (HRT). HRT is extremely effective in treating subjective symptoms and can really improve the quality of life of climacteric women. HRT and dementia: Estrogens are potentially relevant to the pathogenesis and treatment of Alzheimer's disease. The effects of different progestogens on cognitive functions and Alzheimer's disease are largely unknown. The prevention of Alzheimer disease might be a major indication to long term HRT. Large prospective, randomized trials will confirm these preliminary data. HRT and osteoporosis: HRT has been strongly correlated with higher bone mineral density and lower fracture incidence. Definite answers in terms of minimum effective dosages, timing and duration of HRT for fracture prevention are needed. HRT and cardiovascular disease: Different lines of evidence suggest that HRT can exert cardioprotective effects with substantial reduction of morbidity and mortality for cardiovascular disease in postmenopausal women. The effects and the role of progestogens in cardiovascular disease prevention are still debated. Prospective, randomized, controlled studies are needed to assess the impact of different HRT regimens on cardiovascular events. HRT and cancer: The major issue in the relationship between HRT and cancer is breast cancer. Long-term and current HRT use are followed by a slight, though significant increase in the risk of breast cancer. Progestogens can modify the cellular response of normal as well as cancer breasts. The possible protective effect of continuous progestogen addition is very interesting and needs further investigation. Alternative to classical HRT: Selective estrogen receptor modulators (SERM). SERMs such as raloxifene (RAL) are a new class of drugs that exert site specific estrogenic or antiestrogenic effects in different target tissues. RAL prevents bone loss and reduces serum cholesterol in postmenopausal women. In contrast to estrogen RAL does not stimulate breast or uterine tissues. In vitro RAL is highly effective at inhibiting the growth of estrogen-dependent breast adenocarcinoma cells. SERMs are expected to represent a major breakthrough for postmenopausal health. CONCLUSION: HRT can be offered either as a preventive tool or as individualized care on the basis of personal needs. New therapeutic options like the SERMs will offer a substantial medical advancement for the treatment of postmenopausal women.     

Hormone replacement in postmenopausal women: impact of progestogens on autonomic tone and blood pressure regulation

OBJECTIVE: Depressed heart rate variability (HRV) reflects an imbalance of autonomic tone and independently predicts increased cardiovascular risk in patients with congestive heart failure or after acute myocardial infarction. While hormone replacement therapy (HRT) with estrogens beneficially modulates autonomic tone and blood pressure (BP) regulation in postmenopausal women, the impact of concomitant treatment with progestogens remains unclear. DESIGN: In this cross-sectional study, HRV and BP were examined in 62 healthy women (ages 48-71 years) using digital beat-to-beat interval recordings of heart rate and 24-hour ambulatory BP measurements. RESULTS: Demographic parameters did not differ among women without HRT (n = 23), on estrogen (n = 17; ERT), or on progestogen-estrogen containing HRT (n = 22; PERT). Total power of HRV was significantly lower, whereas mean heart rate (HR) was significantly higher among women on PERT group versus controls and ERT (total power: 1611 +/- 146 vs. 2497 +/- 308 and 2472 +/- 348 ms(2); heart rate: 80.7 +/- 1.2 vs. 75.0 +/- 1.4 and 74.0 +/- 2.2 bpm; p < 0.05). In addition, low-frequency power and time-dependent parameters of HRV were lower among women on PERT group versus controls and ERT (p < 0.05). ERT use was associated with reduced systolic and diastolic daytime BP, whereas no significant differences were evident PERT users compared with controls. CONCLUSIONS: Progestogen-containing replacement therapy was associated with increased HR and an attenuation of HRV in postmenopausal women. BP was lower in women on ERT, whereas this effect was offset in the PERT group. These observations could at least partially explain the ambiguous results of progestogen-containing HRT on cardiovascular risk in the Heart and Estrogen/Progestin Replacement Study (HERS).     

The relative effects of progesterone and progestins in hormone replacement therapy

Hormone replacement therapy (HRT) was initially given to protect women against osteoporosis and alleviate menopausal symptoms, such as hot flashes, depression, sleep disturbances, and vaginal dryness. In view of the understanding of oestrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, HRT may also be proposed as a substantial beneficial cardioprotective agent. Progestins, which may be added to oestrogen in combined HRT to reduce the risk of uterine malignancy, have a number of potential adverse effects on the cardiovascular system which could even attenuate the benefit of unopposed oestrogen replacement therapy in post-menopausal women.     

雌激素防治骨质疏松症的研究进展

１９４１年Ａｌｂｒｉｇｈｔ首先提出绝经与骨质疏松之间的关系，５０多年来，大量的临床与实验研究证实，雌激素缺乏是绝经后骨质疏松的重要发病因素。低雌激素状态或绝经后补充雌激素，可以预防雌激素低下引起的骨丢失，并对绝经后的多种改变有防治作用，例如绝经后症状...     

性激素替代治疗与乳腺癌

目前世界范围内乳腺癌发病率呈上升趋势Ｍａｒｉａｎｎｅ指出１９８５年时医学家估计全世界每年出现７２万新病例，预计至２０００年每年将出现１００万新病例［１］之所以出现乳癌发病率增长，其原因是与妇女平均寿命的提高有关，因为４０岁以上妇女乳腺癌的发生率升高...     

HRT as secondary prevention of cardiovascular disease

Objective: To review the evidence of the efficacy of postmenopausal hormone replacement therapy (HRT) in secondary prevention of coronary artery disease or stroke. Results: Although a number of rather large and prolonged non-randomized observational studies have produced convincing and consistent evidence of the efficacy of HRT in the prevention of recurrence of cardiac events, the first randomized, placebo controlled trial (RCT) on heart disease and estrogen replacement study (HERS) reported no benefit of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) in secondary prevention of cardiac events in women with established coronary artery disease. This was supported by RCT reporting no effect of CEE or CEE + MPA on the progress of coronary sclerosis. Similarly, some nonrandomized observational studies have evaluated the risk of recurrent stroke in regard to the use of HRT, and the data are conflicting reporting a reduced or increased risk of recurrence for HRT users. One RCT has shown that low-dose estrogen treatment can only slow down the progression of carotid arteriosclerosis in high-risk postmenopausal women, whereas two other RCTs have shown no benefit (or risk) of using HRT for secondary prevention of ischemic stroke or progression of carotid atherosclerosis. Conclusion: The evidence accumutaed so far shows that HRT has no place in secondary prevention of coronary or carotic artery disease. Its use in these patients must be based on solid nonvascular indications and expected benefits from these causes.     

The prevalence of symptoms possibly related to the climacteric in pre- and postmenopausal women in Linköping,Sweden

BACKGROUND: Some extragenital symptoms have been suggested to be associated with the menopause and thus to be affected by estrogen status. In such case extragenital symptoms may be more frequent in postmenopausal women without hormone replacement therapy (HRT) than in premenopausal women or women using HRT. OBJECTIVE: To assess if the prevalence of a number of extragenital symptoms is higher in postmenopausal women without than with HRT, or in premenopausal women of the same age. MATERIAL AND METHODS: All women aged 53 and 54 years in the community of Link?ping (n=1760) were sent a validated questionnaire about use of HRT, time since last menstruation and about different extragenital symptoms. RESULTS: 1298 (73.8%) women answered the questionnaire and answers from 1180 (67%) women were possible to analyze. Postmenopausal women woke up significantly more often during night than premenopausal, and those without HRT often due to hot flushes and sweating. Women with HRT reported more muscular pain than the others. We found no other significant difference in prevalence of extragenital symptoms between the three groups of women. CONCLUSIONS: Sleeping disorders, arthralgia, xerophthalmia, xerostomia and dry skin are not more prevalent in 53 and 54 years old postmenopausal women without HRT than in women with HRT or in premenopausal women of the same age. It may still be that some of these symptoms are related to estrogen deficiency, but do not develop until some years after menopause. It may also be that women with the most severe symptoms decided to use HRT and thereby decreased symptoms to the same level as in non-users.     

绝经期妇女骨质疏松症与心血管疾病

世界不同地区妇女平均绝经年龄为５０岁。世界银行１９９０年人口调查报告指出，５０岁以上妇女约有４７亿，预计２０３０年将增至１２亿。中国５０岁以上的妇女将占世界总数的２３％，为世界首位。年龄别心血管疾病死亡率妇女低于男子，但随年龄增加至７５岁时妇女与男...     

Estrogen replacement therapy, subsyndromal depression, and orthostatic blood pressure regulation

Although estrogen replacement therapy (ERT) alleviates depressed moods in postmenopausal women, it is not known whether ERT is equally effective in reducing affective and somatic depressive complaints. One of the authors' goals in this study was to examine possible differences between women receiving and not receiving ERT. The authors studied a group of postmenopausal women. Somatic symptoms in the ERT group were significantly lower than in the Non-ERT group. Affective scores were only marginally lower in the ERT group (p = .06). After controlling for affective depression, the advantage of ERT remained significant with respect to somatic levels, but control for somatic levels essentially eliminated the effects of ERT on affective depression values. Second, in response to orthostatic challenge, the change in systolic blood pressure was significantly smaller in the ERT group. Apparently ERT is associated with more effective blood pressure regulation. Thus there are several potential benefits of ERT, despite recent evidence finding several untoward effects of long-term treatment.     

Personal perspective on low-dosage estrogen therapy for postmenopausal women.

OBJECTIVE: As evidenced by results from recent clinical trials and epidemiological studies that have examined the physiological and clinical effects of low levels of estradiol, it is now time to replace the widely held belief that less than the standard dosage of estrogen is without benefit. DESIGN: Review of literature and personal experience. RESULTS: Studies indicate that low-dosage estrogen can relieve vasomotor symptoms, can prevent bone loss, and may reduce the risk of coronary heart disease. However, to achieve these health benefits, long-term estrogen use is required. Women who use low dosages of estrogens are less likely to have unacceptable side effects, such as irregular bleeding, heavy bleeding, or breast tenderness. Thus, long-term continuance of hormone replacement therapy (HRT) may be improved if lower dosages are given, particularly if the HRT regimen is tailored to the needs of the patient. CONCLUSIONS: Although standard-dosage estrogen remains the "gold standard" for HRT, having a low dosage as an alternative regimen can be useful. Attention of clinical researchers should focus on the effects of low-dosage estrogen on osteoporotic fractures and other health outcomes.     

The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms

OBJECTIVE: To evaluate the benefits and risks of hormone replacement therapy (HRT) combined with methyltestosterone (MT) in postmenopausal women with sexual dysfunction. DESIGN: This study was a randomized, double-blind, placebo-controlled and crossover trial. Eighty-five women using HRT were divided into four treatment groups: GI-HRT plus placebo for 4 months; GII-HRT plus MT 2.5mg/day for 4 months; GIII-HRT plus placebo for 2 months and then replaced with HRT plus MT 2.5mg/day for 2 months; GIV-HRT plus MT 2.5mg/day and then replaced with HRT plus placebo for 2 months. Blood was collected at baseline, after 2 months (T1) and 4 months (T2) of treatment for hormone determinations of estradiol, FSH, total and free testosterone, GOT, GPT, glucose, total and fractions of cholesterol and triglycerides. All participants answered clinical questions and a validated questionnaire of modified McCoy's sex scale. RESULTS: The association of HRT with MT 2.5mg/day did not significantly change liver enzymes or increase cardiovascular risk factors. The patients of GII, GIIII and GIV when using MT presented amelioration of sex symptoms, mainly satisfaction and desire (p<0.01); however, GIII at T1 (1.3+/-0.3) presented similar problem score results as compared to GIII at T2 (1.5+/-0.6). CONCLUSION: All data suggest that combined HRT-androgen therapy may be beneficial for postmenopausal women receiving HRT who continue to complain of sexual difficulties or for postmenopausal women with sexual complaints who are not undergoing estrogen therapy.     

The effect of the duration of progestin use on the occurrence of endometrial cancer in postmenopausal women.

OBJECTIVE: Women who have ever used estrogen replacement therapy (ERT), even at a low dose, have an increased incidence of endometrial cancer. The addition of a progestin to ERT reduces the incidence of endometrial cancer. The duration of progestin administration is more important than the dose. DESIGN: A MEDLINE review of the literature was performed using the search terms endometrial cancer, epidemiology, and hormone replacement therapy (HRT). RESULTS: Women who have ever used ERT have an increased incidence of endometrial cancer. The use of HRT for more than 5 years, with a progestin use of <10 days per cycle, has a relative risk = 1.8. Continuous combined HRT, or sequential or cyclic HRT with >10 days of progestin per cycle, appears to decrease the incidence of endometrial cancer to that found in nonusers of HRT. CONCLUSIONS: The use of HRT in postmenopausal women with a uterus reduces the incidence of endometrial cancer. The duration of progestin administration should be 14 days or more per cycle based on recent epidemiologic data.     

A comparative study of transvaginal uterine ultrasound and endometrial biopsy for evaluating the endometrium of postmenopausal women taking hormone replacement therapy.

OBJECTIVE: Compare transvaginal uterine ultrasound and endometrial biopsy in evaluating the endometrium of postmenopausal women who are taking estrogen replacement therapy (ERT) or hormone replacement therapy (HRT; estrogen and progestin). DESIGN: Prospective multicenter study done in the United States with 148 healthy women with an intact uterus. A total of 121 women used hormonal preparations prescribed by personal physicians. Continuous combined HRT regimens, nonoral forms of ERT or HRT, and intrauterine devices were not allowed for 3 months before the study began. Endometrial biopsy samples were taken within 3 days of transvaginal ultrasound measurement. The uterus was scanned transversely and longitudinally. Endometrial thickness was measured at the thickest part of the longitudinal plane. RESULTS: Endometrial thickness ranged from 1.0 to 25.0 mm. The range in 126 women with a normal endometrium (determined by diagnoses of endometrial biopsies) was 1.0-25.0 mm (median, 5.0 mm); in 15 women with an abnormal endometrium, the range was 2.8-23.0 mm (median, 6.2 mm). A significant difference (p = 0.006) in endometrial thickness was seen between the 38 subjects taking ERT and HRT (median, 6.1 mm) with unexpected bleeding or spotting and the 26 untreated women in the control group (median, 4.0 mm). Overall, results were clinically inconclusive. CONCLUSIONS: Results of ultrasound as a screening technique in postmenopausal women who were taking ERT or HRT did not correlate well with results of endometrial biopsy. Unscheduled bleeding in postmenopausal women should be investigated regardless of results of ultrasonographically determined endometrial thickness. Abnormalities may be found with an endometrial thickness of less than 4 mm with or without HRT and even with no bleeding.     

Controversy between estrogen replacement therapy and risk of breast cancer in menopause

At present, no information is available from controlled prospective randomized clinical trials to demonstrate a causal link between estrogen replacement therapy (HRT) and the risk of developing breast cancer. In most epidemiologic studies, HRT is not associated with an major increased risk of breast cancer; thus for women who had used estrogen for 10 years or more, the relative risk of breast cancer is 1.46 which is considered as small magnitude. Clinicians and patients are challenged with the difficult task of balancing the beneficial effects of HRT on cardiovascular and bone disease with the potential adverse effects on the breast. The analyses of the benefits and risks of HRT generally indicate that the benefits of therapy outweigh the risks. In other respect the number of survivors of breast cancer are increasing rapidly because of both early detection and the availability of more effective treatments. This effect will increase the number of hypoestrogenic survivors of breast cancer, a group that might benefit from HRT. However, the decision of using HRT has to be determined between the patient and the physician.     

The comparison of effects of tibolone and conjugated estrogen-medroxyprogesterone acetate therapy on sexual performance in postmenopausal women

OBJECTIVE: To compare the effects of two different postmenopausal regimens on sexual performance. METHODS: A single blind prospective clinical study was planned on fifty natural postmenopausal women with no absolute contraindication for hormone replacement therapy (HRT). A total of 25 women were randomized for tibolone therapy (group T) and the rest 25 for continuous conjugated estrogen (CE) 0. 625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg (group E) for a year. Two women in group T and four women in group E were excluded from the study as they didn't attend the control visit. At baseline and after a year, sexual performance parameters (sexual desire, coital frequency, orgasm frequency, vaginal dryness/dyspareunia) and after therapy subjective well-being, vasomotor symptoms, and side effects were assessed by score method designed by us. RESULTS: Treatment with either preparation significantly improved subjective well-being, vasomotor symptoms and vaginal dryness. The rates of overall side effects between two groups were not found statistically different (P=0.84). Tibolone therapy increased sexual desire and coital frequency (P=0.001, P=0.014). CONCLUSIONS: Both tibolone and continuous combined CE/MPA effectively improve the findings of hypoestrogenism and subjective well being. Moreover, tibolone effectively increases sexual performance. It is seen that tibolone with acceptable androgenic side effects can be an appropriate selection for HRT in postmenopausal women with decreased sexual desire.