Biomedical subjects

P Ibarra de Palacios

Publications and source records attributed to P Ibarra de Palacios.

6 recordsLinked to original sources

PubMed2006

Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: a randomized open-label study.

OBJECTIVES: To establish whether transdermal continuous hormone replacement therapy (HRT) with estrogen/progestogen provides adequate long-term endometrial protection in postmenopausal women over a period of 96 weeks. METHODS: This multicenter, randomized, open-label, parallel-group study evaluated the endometrial effects and overall safety and tolerability of a transdermal matrix patch delivering estradiol (E2) 50 microg/day and norethisterone acetate (NETA) 140 microg/day (Estalis; patches applied twice weekly without intermediate breaks) and a once-daily oral comparator (Kliogest; one tablet containing E2 2 mg/NETA 1 mg) in postmenopausal women. A total of 406 women with an intact uterus, aged 44-69 years, were randomized in the 48-week core phase of the study, and 239 continued into the 48-week extension phase. Subjects were randomized in the ratio 3 : 1 to transdermal or oral E2/NETA treatment. RESULTS: No cases of endometrial hyperplasia or endometrial cancer were reported with either treatment during the core or extension phase. Both treatments were generally well tolerated, with most adverse events (>90%) being mild to moderate, although minor differences in the tolerability profile were observed between treatments. CONCLUSIONS: Continuous combined transdermal HRT with E2/NETA shows no evidence of an increased endometrial hyperplasia or endometrial cancer risk over a 96-week period.

Administration, Cutaneous↗

PubMed2005

Hormone replacement therapy and breast density changes.

OBJECTIVES: To compare the incidence of increased breast density and tenderness in postmenopausal women associated with transdermal (Estalis/Combipatch), Novartis, Basel, Switzerland) and oral (Kliogest), Schering AG, Berlin, Germany) hormone replacement therapy (HRT). METHODS: A total of 202 postmenopausal women were randomized to transdermal or oral HRT. Mammograms obtained at study entry and after 1 year of treatment were assessed for percent breast density by means of the digital segmentation and thresholding technique. Breast tenderness was assessed at each study visit. RESULTS: The mean breast density by ANCOVA after adjusting for screening value at study end was significantly lower for women using Estalis (38.4%, standard error 0.9%) compared with Kliogest (46.9%, standard error 1.5%) (p<0.0001). Significantly fewer women using transdermal HRT had an increase in mammographic breast density or breast tenderness compared to oral HRT. Of the women using transdermal HRT, 39.1% had no change in breast density compared to 15.7% for women using oral HRT. Only 4% of women using transdermal HRT had a marked increase in density (>25%) compared to 15.7% of women using oral HRT. Overall, 36.0% of patients in the transdermal group reported breast tenderness at some point during the 1-year study, compared with 57.6% in the oral HRT group (p=0.0002). CONCLUSION: Transdermal HRT use is associated with a significantly lower incidence of increased mammographic breast density and breast tenderness compared with oral HRT.

Administration, Cutaneous↗

PubMed2002

Comparative study to evaluate skin irritation and adhesion of Estradot and Climara in healthy postmenopausal women.

OBJECTIVES: To compare the local tolerability, adhesion and estradiol delivery of a 5-cm(2) transdermal patch (Estradot), Novartis Pharmaceuticals, Basel, Switzerland) and a 12.5-cm(2) patch (Climara, Berlex Laboratories, Wayne, NJ, USA). METHODS: This was an open-label, randomized, intrapatient, comparative study. One hundred healthy postmenopausal women applied the 50 micro g/day 5-cm(2) patch and the 12.5-cm(2) patch concurrently for 7 days; safety and tolerability were assessed. Twelve women continued to apply the 5-cm(2) and 12.5-cm(2) patches separately for 7 days in a two-way cross-over study, to investigate the reproducibility of estradiol delivery. RESULTS: The proportion of subjects with a clinically significant erythema score was higher with the 12.5-cm(2) patch. The 5-cm(2) patch had a significantly lower incidence of very slight erythema than the larger patch (21.4% vs. 32.3%; p = 0.0028). Overall erythema scores were 0.22 and 0.41, respectively. More 5-cm(2) patches had > 90% adherence than the 12.5-cm(2) patches (87.5% vs. 82.0%, not significant) and fewer became detached (0.5% vs. 3.0%). Both the patches showed reproducible delivery of estradiol. CONCLUSION: The 5-cm(2) patch was associated with less skin irritation and better adherence than the 12.5-cm(2) patch, although the majority of the differences were not significant. The 5-cm(2) patch was well tolerated and showed reproducible estradiol delivery, as did the 12.5-cm(2) patch.

Adhesiveness↗

PubMed2000

Open comparative trial of formestane versus megestrol acetate in postmenopausal patients with advanced breast cancer previously treated with tamoxifen.

The aim of the trial was to compare efficacy and safety of the aromatase inhibitor formestane (250 mg i.m. given every 2 weeks) with the progestin megestrol acetate (160 mg administered orally once daily), as second-line therapy in postmenopausal patients with advanced breast cancer previously treated with tamoxifen. A total of 547 patients were enrolled. Analyses revealed no statistically significant or clinically relevant difference between treatments with respect to time endpoints. In the intent-to-treat analysis, the median values for time to failure and overall survival for formestane were 169 and 561 days, respectively. The corresponding values for megestrol acetate were 169 days and 597 days, respectively. Overall response rates were comparable for formestane and megestrol acetate (16.3% vs 20.3%). Formestane was better tolerated than megestrol acetate. In the megestrol acetate group, cardiovascular events, weight increase, and vaginal haemorrhage were significantly more frequent than in the formestane group. Thus, formestane is a suitable alternative to progestins in patients previously treated with tamoxifen.

Journal Article↗

PubMed1997

An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates.

We studied the acute phase response, including specific cytokine production, [interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha(TNF alpha)] following a single dose of Aredia (disodium pamidronate) in patients with increased bone turnover and, in vitro, the role played by specific cytokines in the acute-phase reaction which may follow the administration of aminobisphosphonates. An in vivo exploratory study was done on 24 in- and outpatients with increased bone turnover given a single intravenous dose of pamidronate 60 mg. Measurements were taken at baseline and at 24, 48, and 72 hours. The main outcome measures were changes from baseline in serum IL-1, IL-6, and TNF alpha. In addition, C-reactive protein (CRP), white blood cell count (WCC), lymphocyte count, and elastase concentration were measured. Symptomatic evaluation was made of fever, bone pain, and rigors. In vitro, whole blood from eight healthy volunteers was exposed to various concentrations of the three bisphosphonates--pamidronate, clodronate, and zoledronate. Measurements were taken immediately before and at 3, 6, and 10 hours after exposure to drugs. The main outcome measures were changes in serum IL-1, IL-6, and TNF alpha. In vivo, there was a statistically significant (P < 0.001) increase in median values of TNF alpha in all post-baseline measurements. Median values for IL-6 also showed a significant (P < 0.001) increase at 24 hours after dosing. There were no statistically significant changes in median IL-1 values. Few patients showed any change from baseline in total WCC or in lymphocyte count, but 62.5% of patients with normal range baseline values for CRP increased to above normal levels after treatment. Fourteen patients experienced fever; 2 reported rigors. There was no correlation between fever and changes in cytokines. There were no serious adverse experiences or premature discontinuations due to poor tolerability, and 91% of the patients expressed willingness to receive pamidronate again. In vitro, an increase in TNF alpha and a mild increase in IL-6 was seen with all bisphosphonates, with the greatest effects seen with the highest concentration of both pamidronate and zoledronate. No changes were observed in IL-1 with any agent. Significant changes in both TNF alpha and IL-6 were observed within 3 days of a single dose of pamidronate in patients treated for the first time confirming previous findings. However, the lack of change in IL-1 in vivo and in vitro does not support the hypothesis that this cytokine plays a major role in the acute phase reaction. The cellular mechanism of the interaction among aminobisphosphonates, IL-6, and TNF alpha requires further investigations. The results of the in vitro study are consistent with the in vivo findings.

Acute-Phase Reaction↗

PubMed1989

Oestrogen replacement therapy and cardiovascular disease in post-menopausal women. A review.

The possible role played by oestrogens in modifying the occurrence of ischaemic heart disease (IHD) in particular and cardiovascular disease (CVD) in general in post-menopausal women has long been controversial. Analysis of the literature reveals a difference between the findings of epidemiological studies published before 1980 and those published more recently. In the former, it was reported that the risk in women using oestrogen replacement therapy (ERT) either remained unchanged or increased in relation to that in non-users. In the latter, the trend changed and ERT was shown to have a definite protective effect. These contradictory results might be explained by a change in prescribing habits, involving the use of lower oestrogen doses and the selection of women with no CVD risk factors as recipients of long-term ERT. The protective effects of ERT have been attributed to metabolic changes induced by oestrogens, namely the increase in high density lipoprotein (HDL) cholesterol observed after oral therapy. Recently, long-term studies using non-oral oestrogens delivered either by implant, or the percutaneous or transdermal routes have indicated the same favourable changes in lipid profiles as seen with oral ERT, provided follow-up is maintained for at least 6 mth. Factors other than lipids that are involved in CVD should also be evaluated in order to clarify the mechanism via which ERT affords cardiovascular protection in post-menopausal women.

Cardiovascular Diseases↗