ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

While the benefits of progestogen use in hormone replacement therapy (HRT) are well recognized as far as endometrial protection is concerned, their risks and drawbacks have generated controversial articles.Several risks are attributed to progestogens as a class-effect; however, the progestogens used in HRT have varying pharmacological properties and do not induce the same side effects. Natural progesterone (P) and some of its derivatives, such as the 19-norprogesterones (Nestorone, nomegestrol acetate, trimegestone), do not bind to the androgen receptor and, hence, do not exert androgenic side effects. Newly synthesized molecules such as drospirenone or dienogest have no androgenic effect but do have a partial antiandrogenic effect. Drospirenone derives from spironolactone and binds to the mineralocorticoid receptor.When the cardiovascular risk factors are considered, some molecules with a higher androgenic potency than others attenuate the beneficial effects of estrogens on the lipid profile as well as the vasomotion. On the other hand, other progestogens devoid of androgenic properties do not exert these deleterious effects. The epidemiological data do not suggest any negative effect of the progestogens administered together with estrogens on cardiovascular morbidity or mortality. However, recent results suggest that in women with established coronary heart disease, HRT may not protect against further heart attacks when the progestogen selected possesses androgenic properties.The data related to the progestogen effect on breast tissue has been interpreted differently from country to country. However, it has been admitted that, according to the type of progestogen used and the dose and duration of its application, a predominant antiproliferative effect is observed in the human breast cells. As far as breast cancer risk is concerned, most epidemiological studies do not suggest any significant difference between the estrogens given alone or combined with progestogens in HRT.Complying with the classic contraindications of HRT and selecting molecules devoid of estrogenic, androgenic, or glucocorticoid effect should allow a larger use of the progestins without any major drawback.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveThis study was designed to compare the bleeding profiles of conjugated equine estrogens 0.625 mg in combination with 2.5 mg medroxyprogesterone acetate (Prempro; CEE/MPA group), the most widely prescribed continuous combined hormone replacement therapy (CCHRT) in the United States, with 17&bgr;-estradiol 1 mg combined with 0.5 mg norethindrone acetate (Activella; E2/NETA group), a newly available CCHRT preparation, over a 6-month period.DesignThis study was a prospective, randomized, multicenter, double-blind, controlled trial. A total of 438 healthy postmenopausal women were randomized and received treatment (Activellan= 217, Prempron= 221). Each woman recorded bleeding diaries daily. Total cholesterol, triglycerides, and endometrial biopsies were obtained at screening and end-of-trial visits.ResultsThe more favorable bleeding profile was found in the E2/NETA (Activella) group. The differences in bleeding patterns were most marked in the first 3 months of treatment in women who were 1–2 years from last menses, with no bleeding in 71.4% vs. 40.0%; (p= 0.005) and with no bleeding and no spotting in 54.8% vs. 17.1%; (p= 0.001). Triglycerides fell by 8.5% in the E2/NETA group and increased by 11.7% in the CEE/MPA group (p< 0.001). Total cholesterol declined by 9.1% and 6.9%, respectively.ConclusionThe most important factor in the continuation of HRT is uterine bleeding. E2/NETA has significantly less bleeding than the most commonly prescribed CCHRT CEE/MPA, therefore; E2/NETA should be associated with improved continuation rates. The patient taking E2/NETA will receive effective treatment for her menopausal symptoms with less bleeding.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The past and possible future roles for hormone use to prevent or encourage pregnancy and to manage or prevent menopause are considered. Beginning in the 1880s, gonadal extracts were used for 50 years to improve health and vigor; evidence for the benefit of these extracts was lacking. Oral contraceptives revolutionized women's lives in the 1960s but had side effects unsuspected until after marketing. Hormone replacement therapy, used for 50 years without large clinical trials of disease outcomes, now proves to have rather similar side effects. Physicians and politicians played interesting roles in their initial distrust and later embrace of hormones. Future uses of sex hormones are likely to be viewed as overmedicalization initially, and time will tell whether these uses are healthy or merely controversial.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo characterize premenopausal menstrual regularity and the patterns of divergence from regularity associated with the approach of the final menstrual period.DesignTwo samples of individual cycle length sequences contributed by participants in a population-based longitudinal study of the menopausal transition were examined. The first sample, of “early” sequences, is used to characterize menstrual regularity. The second shows how cycle length patterns change as the final menstrual period (FMP) is approached. Regression slopes are used to measure trend in cycle length, and changes in cycle length variability are registered by a simply calculated measure, the “running range.”ResultsSequences in the early cycles sample rarely varied outside the 21–35 day range and did not show a rising or falling trend. In contrast, pre-FMP sequences generally became increasingly variable in length, while rising above 35 days in mean during the last 10 cycles. The variability measure remained below 40 days throughout the early sequences, but characteristically rose above 42 days during sequences including the last 20 pre-FMP cycles. In early sequences, but not in pre-FMP sequences, long and short cycles tended to alternate.ConclusionsIncreased variability is the dominant feature of cycle length pattern for most women as their final menstrual period approaches. Underlying this is a steady trend toward mean cycle lengths above 35 days. An indicator of the approach of menopause is a rise in running range of cycle lengths to 42 days.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTibolone is used to prevent osteoporosis and to treat climacteric symptoms. The objectives of these studies were to measure and compare the effects of tibolone with hormone replacement therapy on coronary artery vascular reactivity and myocardial function and to relate these outcomes to treatment-induced plasma lipid/lipoprotein concentrations and atherosclerosis.DesignOne hundred forty-eight adult ovariectomized cynomolgus monkeys were fed an atherogenic diet for 24 months while receiving one of five oral treatments: no treatment (control,n= 31); conjugated equine estrogens (CEE), given at the equivalent of 0.625 mg/day (n= 27); CEE (same dose) plus medroxyprogesterone acetate (MPA), given at the equivalent of 2.5 mg/day (n= 29); low-dose tibolone (LoTib; 0.625 mg/day equivalent,n= 30); or high-dose tibolone (HiTib; 2.5 mg/day equivalent,n= 31).ResultsQuantitative coronary angiography showed that endothelium-mediated dilation was enhanced (17.5 ± 5%,p= 0.002) in the CEE-treated group (but not other treatment groups) compared with the control. Both doses of tibolone and CEE reduced the incidence of dobutamine-induced ST-segment depression (LoTib: 33%, HiTib 25%, and CEE: 23%) compared to the control (79%) (p= <0.05). Neither vascular reactivity nor dobutamine-induced myocardial ischemia were associated with treatment-induced changes in atherosclerosis or plasma lipid/lipoprotein concentrations.ConclusionsTibolone, unlike CEE, has no benefit for endothelium-mediated dilation. Despite these differences, both tibolone and CEE reduced the incidence of myocardial ischemia, whereas CEE+MPA had no effect. It is speculated that tibolone may have direct effects on the myocardium that protect against myocardial ischemia.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivePostmenopausal hormone replacement therapy (HRT) has been associated with reduced risk of cardiovascular disease; however, the mechanisms remain obscure, and it is not known whether this applies to regimens containing both estrogen and progestin. One possibility is that estrogen would act via enhancement of cardiac autonomic regulation.DesignIn this prospective, controlled study of 6-months duration, 22 osteoporotic, postmenopausal women in the intervention group were treated with combined estradiol hemihydrate corresponding to estradiol 2 mg and norethisterone acetate 1 mg with or without clodronate (HRT group). Nine women in the control group received clodronate only. Indices of heart rate variability (HRV) by power spectral analyses and baroreceptor sensitivity (BRS) by phenylephrine test were measured before and after 3 and 6 months of treatment.ResultsThe total power of HRV remained identical within the groups, although it was higher at 3 and 6-month measurements in the control group than the HRT group. This was mainly due to lower very low frequency and high frequency power in the HRT group. However, no changes in the low frequency/high frequency-ratio of HRV, an index of sympathovagal balance, were observed between and within the groups. Further, during the intervention, no significant changes in BRS (baseline and 6 months: 5.0 ± 2.1 and 5.1 ± 2.5 ms/mmHg) within the HRT group was observed.ConclusionsThe impact of estrogen and progesterone on cardiac autonomic regulation seems to be quite modest. Therefore, cardiac morbidity and mortality are probably not mediated by their effects on cardiac autonomic regulation. However, the effects of estrogen alone or more selective estrogen receptor modulators need yet to be clarified in future studies.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveShort-term estrogen therapy improves endothelial function in postmenopausal women. However, there are few reports on its long-term effects on endothelial function and carotid intima-media thickness. Further, we determined whether a reduced dosage of estrogen may maintain its beneficial effects.DesignEighteen postmenopausal women (53.7±1.1 years) who had been diagnosed as having osteoporosis were enrolled. Among them, 11 women were prescribed oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg per day, and 7 women were prescribed an oral calcium supplement as the control group. Each patient decided whether she would take hormone replacement therapy or a calcium supplement. We performed ultrasound measurement of endothelial function of the brachial artery and carotid intima-media thickness. Examinations were scheduled to be performed pre-therapy and after 3, 6, 12, 18, 24, and 36 months of therapy.ResultsAfter three years of therapy, 6 women in the hormone replacement therapy group agreed to take half the dose of oral conjugated estrogen. Improvement of flow-mediated dilatation was observed at 3 months and the improvement was preserved up to 36 months. A similar improvement was also observed while women were on hormone replacement therapy even at the reduced dosage. Intima-media thickness of the common carotid artery in the control group increased after 12 months, which was not observed in the hormone replacement therapy group.ConclusionsOur results indicate that even at half the dose of estrogen, hormone replacement therapy may improve endothelial function and prevent the progression of carotid intima-media thickening in postmenopausal women.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo investigate whether the administration of transdermal estradiol is capable of modifying circulating levels of leptin.DesignForty postmenopausal women randomly received in a double-blind fashion, a transdermal patch containing either placebo or estradiol (50 &mgr;g/day). After 2 months of treatment, they were switched to the alternate treatment for another 2 months. Leptin levels were measured at the end of the placebo and estradiol administration. In a subset of 28 women an evaluation of body composition via bioelectrical impedance and an oral glucose tolerance test (OGTT; 75 g) were also performed at the end of the placebo and estradiol administration. Glucose, insulin, and leptin levels were measured in all OGTT samples.ResultsLeptin levels were related directly to body mass index (BMI), fat mass, and insulin, and inversely related to lean mass. In comparison to placebo, transdermal estradiol increased estradiol (from 77.8 ± 8.4 pmol/l to 183.1 ± 20.9 pmol/l;p< 0.0001) but did not significantly modify leptin (19.1 ± 2.4 &mgr;g/l vs. 18.6 ± 2 &mgr;g/l) or BMI. Estradiol did not modify fat mass or lean mass, significantly increased intracellular water (31.1 ± 0.7% vs. 37.2 ± 2.3%,p< 0.05), and decreased extracellular water (40.5 ± 0.7% vs. 36.3 ± 1.7%;p< 0.04). Leptin did not increase during OGTT, but a significant decrease, linearly related to BMI (r= 0.519;p= 0.0189), was observed at the end of the test.ConclusionsLow doses of transdermal estradiol exert no influence on fasting leptin levels or BMI. The possibility that different doses of estradiol exert a more pronounced effect on circulating leptin needs to be addressed in comparative studies.

ISSN:1072-3714    

出版商:OVID    

年代:2002

数据来源: OVID