Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome
Nicholas A. CataldoFahim AbbasiTracey McLaughlinMarina BasinaPatricia Y. FechnerLinda C. GiudiceGerald M. Reaven
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BACKGROUND: Insulin sensitizers have favourable metabolic and ovarian effects in polycystic ovary syndrome (PCOS). This study examined rosiglitazone, a thiazolidinedione, in PCOS. METHODS: In a prospective, open-label study, the effects of rosiglitazone on metabolism and ovarian function were examined in 42 non-diabetic women with PCOS classified according to the National Institute of Child Health and Human Development criteria and insulin resistance (IR) by steady-state plasma glucose (SSPG) ≥10 mmol/l on octreotide-modified insulin suppression testing. Participants were randomized to rosiglitazone 2, 4 or 8 mg daily for 12 weeks. Endpoints included ovulation and menstrual pattern; serum testosterone, sex hormone-binding globulin (SHBG), and LH; and changes in IR and glucose–insulin responses on 8 h mixed-meal profile. RESULTS: After rosiglitazone 8 mg daily for 12 weeks, SSPG declined and insulinaemia fell by 46%; lower doses gave lesser effects. Serum LH, total and free testosterone were unchanged; SHBG increased. With rosiglitazone, ovulation occurred in 23/42 women (55%), without significant dose dependence. Both before and during treatment, ovulators on rosiglitazone had lower circulating insulin and free testosterone and higher SHBG than non-ovulators. Testosterone declined only in a subgroup of ovulators with early vaginal bleeding after starting rosiglitazone. CONCLUSIONS: Rosiglitazone in insulin-resistant PCOS promoted ovulation and dose-dependently decreased IR and insulinaemia; ovulators had lower circulating insulin and testosterone.Keywords:
Rosiglitazone
To report 2 cases of very low high-density lipoprotein cholesterol (HDL-C) levels associated with rosiglitazone therapy.Two patients with type 2 diabetes taking rosiglitazone for glycemic control developed paradoxically low HDL-C levels during rosiglitazone therapy. In the first patient, the HDL-C level decreased from 33 to 11.6 mg/dL after 8 months of therapy. The second patient's HDL-C level decreased from the baseline level of 44.8 mg/dL to 19.7 mg/dL after 4 months of rosiglitazone use. These abnormalities resolved on discontinuation of rosiglitazone and were not observed when the patients were treated with pioglitazone. The patients had no changes to other drug therapy or medical conditions known to affect lipid metabolism during treatment with rosiglitazone.Thiazolidinediones, insulin sensitizers widely used in the treatment of type 2 diabetes, have been reported to have beneficial effects on lipids, such as triglyceride lowering and HDL-C elevation, in addition to their glucose-lowering effects. It has been suggested that rosiglitazone and pioglitazone, the 2 currently available thiazolidinediones, may differ in their effects on lipids. As of July 2006, a total of 8 cases of paradoxical lowering of plasma HDL-C associated with rosiglitazone have now been reported. Based on use of the Naranjo probability scale, the 2 cases presented here were probably associated with rosiglitazone. The duration of therapy may be important in this paradoxical effect.Rosiglitazone is associated with a paradoxical decrease in HDL-C levels in patients with type 2 diabetes. In patients receiving rosiglitazone, a baseline lipid panel should be performed and lipid values should be monitored during the course of therapy.
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The progress of clinical study and adverse events of thiazolidine rosiglitazone were reviewed in this article. The clinical effect iveness of rosiglitazone in combination with other antidiabetic agents was better than that of rosiglitazone as monotherapy. Furthermore, the patients with type-2 diabetes mellitus administered with rosiglitazone, who had been previously treated with dietotherapy only, had better effect iveness than those who had been previously treated with one or more other antidiabetic agents. In addition, rosiglitazone has light adverse events and does not cause significant hepatic dysfunction.
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The thiazolidinediones (TZDs) are a class of oral drugs used for the management of type 2 diabetes mellitus and act as ligands for the transcription factor Peroxisome Proliferator-Activated Receptor gamma (PPARγ). Rosiglitazone, an example of TZD, is an anti-diabetic agent acting as a potent insulin sensitizer and is used clinically to enhance insulin-stimulated glucose uptake in tissues. However, in spite of the beneficial effects of TZDs in management of type 2 diabetes, the safety of rosiglitazone has recently been called into question. The debate about the risks associated with rosiglitazone therapy heightened in 2007, when it was reported that rosiglitazone was associated with an increase risk of myocardial infarction and death from cardiovascular causes. The cardiovascular risk associated with rosiglitazone use remains to be further elucidated, but there are several reasonable hypotheses.Keywords: Thiazolidinediones; Rosiglitazone; Type 2 Diabetes; Cardiovascular risk
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Rosiglitazone is one of thiazolidinediones (TZD),an antidiabetic agent which improves insulin sensitivity,but the cardiovascular safety of the drug remains controversial.The new re-evaluation of the RECORD trial has suggested that rosiglitazone-containing drugs do not show an increased risk of heart attack compared to the standard type 2 diabetes medicines,such as mefformin and sulfonylurea.The post hoc analysis of the BARI 2D also indicates that rosiglitazone may not relate with the increased risk of major ischemic cardiovascular events.According to these new results,there is no clear evidence that rosiglitazone may increase cardiovascular risk.The U.S.Food and Drug Administration announced in July 2013 that it is requiring the removal of some prescribing and dispensing restrictions for rosiglitazone-containing diabetes medicines.
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Rosiglitazone; Diabetes mellitus, type 2 ; Cardiovascular events; Safety
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본 연구는 인술린비의존성 당뇨병환자의 경구용 혈당강 하제로 사용되는 rosiglitazone이 in vivo 골조직 collagen의 신생율에 미치는 영향을 측정하기 위해 수행되었다. 저지방 식이군과 고지방식이군은 각각 총열량의 10%와 45%를 지방으로 공급하였고 rosiglitazone 첨가군은 고지방식이에 rosiglitazone을 6.3 ㎍/kcal로 조절하여 공급하였다. 또한 collagen의 신생율을 안정동위원소비 질량분석법으로 측정하기 위하여 99.9% ²H₂O를 일시 복강주입하여 실험동물 체액의 ²H₂O 수준을 2.0~2.5%에 도달시킨 후 4% ²H₂O를 음용으로 3주 동안 계속 공급하였다. 체중증가량 및 식이섭취량은 각 실험군간에 유의한 차이가 없었으나 rosiglitazone첨가군이 다른 실험군에 비하여 높은 경향을 보였고, 체지방함량은 고지방식에 rosiglitazone를 첨가한 군이 다른 군에 비하여 유의한 증가를 보였다. 고지방식이군이 저지방식이군보다 골조직 collagen의 신생율이 낮았고 rosiglitazone의 첨가는 collagen의 신생율을 더욱 감소시켰으나 유의한 차이를 보이지는 않았다.
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In order to investigate the androgen and sex hormone binding globulin (SHBG) levels in the polycystic ovary, we compared the total testosterone, free testosterone and SHBG levels in three patterns of polycystic ovary diagnosed with transvaginal ultrasonography (18 in group 1, fewer than 5 cysts identified; 16 in group 2, 5-10 cysts; and 27 in group 3, 10 or more). Free testosterone, but not total testosterone, significantly correlated with body mass index. Androgen levels were found to increase and SHBG levels to decrease with increases in the amount of ovarian cysts, and the evaluation of free testosterone was important in diagnosing the polycystic ovary syndrome.
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Objective To investigate whether rosiglitazone compound formula could eliminate the side effects of rosiglitazone and to investigate the possible mechanism. Methods We researched the blood volume, kidney and heart function after administering rosiglitazone formula in normal rats by measuring different biochemical indicators. All the data were statisticaly analyzed by SPSS 13.0. Results Rosiglitazone decreased HCT, ALB and ALD concentration, and impacted electrolyte concentration. Luckily, rosiglitazone formula RSGF group were without above phenomena. Conclusion Rosiglitazone may induce side effects by regulating serum ALB and ALD concentration, while rosiglitazone compound formula can eliminate the side effects of rosiglitazone.
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Men with low testosterone concentrations are usually hypogonadal. However, because variations in the testosterone transport protein, sex hormone-binding globulin (SHBG), directly influence the total testosterone concentration, confirmation of a low testosterone with a measurement of free testosterone or "bioavailable" testosterone (BAT) is recommended. In the present study, we examined the relationship of SHBG with free testosterone (Coat-A-Count assay, Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who participated in a study of the metabolic determinants of body composition. As expected, total testosterone was strongly positively correlated with SHBG among men (r = 0.68; P <0.01). Although the BAT was independent of SHBG in men (r = 0.02), SHBG was an important predictor of free testosterone (r = 0.62; P <0.01). In contrast, in women serum concentrations of total testosterone (r = -0.26; P = 0.17), free testosterone (r = -0.30; P = 0.17), and BAT (r = -0.46; P = 0.013) all tended to be lower with increasing SHBG. Free testosterone was nearly perfectly positively correlated with total testosterone (r = 0.97) in men, among whom free testosterone represented a relatively constant percentage of the total testosterone (0.5-0.65%), and the percentage of free testosterone was unrelated to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the total testosterone concentration, is determined in part by plasma SHBG. Accordingly, androgen deficiency may be misclassified with this assay in men with low SHBG. Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related.
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Objective To explore the relationship of ovulation outcome in patients with polycystic ovary syndrome(PCOS)and related factors.Methods Used Clomifene to induce ovulation in patients with polycystic ovary syndrome,and analyzed the effect of the success of ovulation induction in patients in the ovulation cycle,age,body mass index,base hormone levels,menstrual type,marital status and other factors influence the outcome of their ovulation.Results The influence of age to ovulation outcome in patients with pelycystic ovary syndrome was not significant (P＞0.05).And body mass index,base hormone levels,menstrual type,marital status was significant on the outcome of ovulation(all P＜0.05).Conclusion Clomifene ovulation induction outcome in patients with polycystie ovary syndrome and body mass index,base hormone levels,menstrual status type and other factors were related to marriage and child rearing.
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Polycystic ovary syndrome; Ovulation Induction
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