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Biomedical subjects

M J van der Mooren

Publications and source records attributed to M J van der Mooren.

At least 19 recordsLinked to original sources
PubMed2006

No increase in C-reactive protein levels during intranasal compared to oral hormone therapy in healthy post-menopausal women.

BACKGROUND: Inflammation plays an important role in the development of atherosclerotic disease. Oral post-menopausal hormone therapy increases serum C-reactive protein (CRP) levels. This study compared the effects of intranasal and oral administration of 17beta-estradiol (E2) combined with norethisterone acetate (NETA) on markers of inflammation in healthy post-menopausal women. METHODS: Ninety healthy post-menopausal women (age 56.6 +/- 4.7 years) participated in this 1-year trial. After computerized block randomization, they daily received, in a double-blind fashion, either intranasal E2/NET [175 microg/275 microg (n = 47)] or oral E2/NETA [1 mg/0.5 mg (n = 43)]. Concentrations of high sensitivity CRP and adhesion molecules were measured at baseline and after 12, 24 and 52 weeks of treatment. RESULTS: CRP levels were increased (P = 0.001) in the oral but not in the intranasal group. The increase in the oral group was highest at week 12 (64.9%) and was larger (P < 0.01) compared with the non-significant increase (8.6%) found in the intranasal group. Both groups showed decreases (P < 0.001) in soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM) and sE-selectin. The decreases were larger (P < 0.01) in the oral than in the intranasal group. CONCLUSION: Intranasal E2/NET therapy did not significantly increase CRP levels, in contrast to the increase observed in the oral E2/NETA treatment group. Both intranasal and oral therapy lowered plasma concentrations of adhesion molecules, however, more so in the oral group.

Administration, Intranasal↗
PubMed2006

Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study.

OBJECTIVE: To compare the effects of oral and transdermal hormone therapy (HT) on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in postmenopausal women. DESIGN: In a multicentre, placebo-controlled, double-blind study, 152 hysterectomized healthy women were randomized to receive daily transdermal 17beta-oestradiol (tE2, n = 33), or oral micronized 17beta-oestradiol either unopposed (oE2, n = 37), or continuous combined with gestodene (oE2 + G, n = 33), or placebo (n = 49) for 13, 28-day treatment cycles. Plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured at baseline and in treatment cycles 4 and 13 with a high-performance liquid chromatography method. RESULTS: After 13 cycles all active treatment groups showed a significant reduction in ADMA compared with placebo: tE2, -4.0% (95% CI: -7.5 to -0.6%); oE2, -7.7% (95% CI: -10.9 to -4.4%) and oE2 + G, -7.5% (95% CI: -10.8 to -4.3%). ancova showed a significantly larger reduction in the oral groups compared with the transdermal group (tE2 vs. oE2 and tE2 vs. oE2 + G, both P < 0.01). Oral, but not transdermal treatment, significantly reduced arginine compared with placebo. All active treatments reduced SDMA; however, this was only statistically significant in the oE2 group. CONCLUSION: Reduction of ADMA was more pronounced after oral than after tE2 administration. Adding gestodene to oral 17beta-oestradiol did not alter the reduction of ADMA. The clinical implications of these findings remain uncertain; however, the decrease of ADMA by 17beta-oestradiol could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal HT.

Administration, Cutaneous↗
PubMed2005

Oral estradiol decreases plasma homocysteine, vitamin B6, and albumin in postmenopausal women but does not change the whole-body homocysteine remethylation and transmethylation flux.

Estrogens, both endogenous and exogenous, lower the fasting levels of the independent risk factor for cardiovascular disease homocysteine. The mechanism behind this observation remains unclear. In a randomized, placebo-controlled, double-blind study, 25 postmenopausal women with a screening homocysteine concentration above 10 micromol/liter were included. We investigated the influence on homocysteine levels of a 3-month treatment with a daily oral dose of 4 mg 17beta-estradiol (ET) or 4 mg ET combined with 10 mg dydrogesterone (EPT); the comparison group received placebo treatment. We performed primed continuous infusions of L-[2H3-methyl-13C]methionine to assess steady-state flux rates of transmethylation, remethylation, and transsulfuration. Homocysteine concentration relationships with S-adenosylmethionine, S-adenosylhomocysteine, creatinine, albumin, vitamins B6 and B12, and folate status were determined as well. The mean change from baseline in homocysteine concentration by both treatments compared with placebo (ET, -13%; EPT, -10%) was accompanied by a decrease in the concentration of vitamin B6 (ET, -25%; EPT, -38%) and albumin (ET, -7%; EPT, -11%). No significant changes in flux rates were observed. In a .multiltivariate analysis, changes in homocysteine concentration were related to changes in albumin concentration. No relation to other variables was observed. We conclude that the ET- and EPT-induced homocysteine changes in this study were not accompanied by a significant change in methionine-homocysteine flux rates and hypothesize that an estrogen-induced lowering of homocysteine levels is primarily part of a change in albumin metabolism.

Aged↗
PubMed2004

Hormone replacement influences homocysteine levels in the methionine-loading test: a randomized placebo controlled trial in postmenopausal women.

OBJECTIVE: To investigate the mechanism by which exogenous oestrogen influences the homocysteine metabolism in postmenopausal women. STUDY DESIGN: A randomized placebo controlled trial in which a methionine-loading test was performed, in 25 healthy postmenopausal women, before and after a 12-week oral treatment with placebo or daily 4 mg 17beta-estradiol with (HRT) or without (ERT) 10 mg dydrogesterone. Fasting and post-load homocysteine as well as Vitamins B(6), B(12) and folate were determined. RESULTS: In both treatment groups a significant 12% decrease in fasting homocysteine was observed. This decrease was accompanied by a post-load homocysteine increase of more than 20%. Vitamin B(6) values were decreased by more than 25%. CONCLUSION: The hormone therapy induced lowering of fasting homocysteine and Vitamin B(6) levels and an increase in post-load homocysteine, supporting the hypothesis that homocysteine-methionine metabolism is modulated by hormone therapy in postmenopausal women.

Analysis of Variance↗
PubMed2004

The Million Women Study: a licence to kill other investigations?

The Million Women Study (MWS), published in the summer of 2003, has suggested unexpected high risks for invasive breast cancer in women using postmenopausal hormone therapy (PHT). Recent reports from randomised controlled trials (RCTs) have demonstrated that long-term combined PHT is associated with a small risk increase for invasive breast cancer, but not for death due to breast cancer. The observational design of the MWS has made this study subject to several biases, that can easily explain the discrepancy with the observations done in RCTs and several other large observational studies. It is concluded that the hormone fear that was caused by the MWS, and augmented by some professionals and the media, was unjustifiable.

Breast Neoplasms↗
PubMed2003

A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels.

OBJECTIVE: To assess the effect of transdermal vs. oral administration of E2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. DESIGN: Prospective, double-blind, double-dummy, placebo-controlled study. SETTING: Outpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. PATIENT(S): One hundred fifty-two healthy hysterectomized postmenopausal women. INTERVENTION(S): Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17beta-E2, 50 microg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 microg (n = 33), followed by four cycles of placebo in each group. MAIN OUTCOME MEASURE(S): Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. RESULT(S): Mean (+/-SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 +/- 2.5 micromol/L vs. 8.2 +/- 2.0 micromol/L; mean change, -7.6%). Homocystine values in the oral E2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 +/- 1.6 micromol/L vs. 8.6 +/- 2.0 micromol/L; mean change, -4.4%). No significant changes were observed in the transdermal E2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. CONCLUSION(S): Oral E2 therapy reduced the homocysteine concentration more than did therapy with transdermal E2 or oral E2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.

Administration, Cutaneous↗
PubMed2003

Estrogens, homocysteine, vasodilatation and menopause: basic mechanisms, interactions and clinical implications.

Estrogens influence the independent cardiovascular risk factor homocysteine as well as vasodilatation. Homocysteine alone also influences vasodilatation, indicating a relational triangle that seems important in interpreting the isolated effects of estrogens on homocysteine metabolism and vasoreactivity. This paper gives an overview of the current understanding regarding vasoreactivity, homocysteine metabolism and the role of estrogens. This is placed against the background of the clinical trials on the effect of postmenopausal hormone replacement therapy on homocysteine levels and addresses the importance of the interaction between homocysteine, estrogens and vasoreactivity.

Cardiovascular Diseases↗
PubMed2002

Effects of hormone replacement therapy on blood platelets.

BACKGROUND: Hormone replacement therapy (HRT) increases the risk of cardiovascular morbidity in postmenopausal women under certain circumstances. Part of this effect may be the result of the influence of HRT on blood platelets. We studied the effect of short-term oral hormone replacement therapy (unopposed oestradiol or sequentially combined oestradiol and trimegestone or dydrogesterone) on platelet activation parameters in healthy postmenopausal women. DESIGN: We designed a prospective, randomised, placebo-controlled 12-week study. Sixty healthy, normotensive, nonhysterectomised, postmenopausal women received daily micronised oestradiol (E2) 2 mg (n = 16), or 2 mg E2 daily sequentially combined with either trimegestone 0.5 mg daily (n = 14) or dydrogesterone 10 mg daily (n = 14), or placebo (n = 16). Data on platelet activation were collected at baseline and after 12 weeks of treatment using flow cytometry. RESULTS: Twelve weeks of treatment with combined HRT was associated with an increase in platelet activation parameters P-selectin and glycoprotein 53 (by 17% and 14%, respectively, P = 0.04 vs. the placebo group for both comparisons), suggesting alpha granule and lysosome degranulation. E2 replacement therapy was associated with an increase in P-selectin labelling by 22% (P = 0.04 vs. the placebo group). CONCLUSION: Short-term treatment with oestradiol or combined HRT increases the amount of circulating activated platelets as measured by flow cytometry. This could be a mechanism by which short-term HRT might increase the risk of thrombosis.

Antigens, CD↗
PubMed2002

Effects of transdermal and oral oestrogen replacement therapy on C-reactive protein levels in postmenopausal women: a randomised, placebo-controlled trial.

To investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), we performed a randomised, double-blind, double-dummy, placebo-controlled, 15-month study. One hundred and fifty-two healthy hysterectomised postmenopausal women received daily either placebo (n = 49), or transdermal 17beta-oestradiol (E(2)) 50 micro g (tE(2) group, n = 33), or oral E(2) 1 mg (oE(2) group, n = 37), or oral E(2) 1 mg combined with gestodene 25 micro g (oE(2) + G group, n = 33) for thirteen 28-day treatment cycles, followed by four cycles placebo for each group. Data were collected at baseline and in cycles 4, 13 and 17. In cycle 13, CRP was significantly increased in the oE(2) group compared to placebo (P = 0.004). The median percentage change from baseline versus placebo was +75% (P <0.001). In cycle 17, significantly lower values were observed in the oE(2) group compared to cycle 13 and to the placebo group (-49%, P <0.001). There were no significant changes versus placebo in the other groups. In conclusion, oral E(2) significantly increased CRP levels. This change was larger than the increase found during oral E(2) + G. Transdermal E(2) did not affect CRP levels.

Administration, Cutaneous↗
PubMed2001

Perspectives in hormone replacement therapy.

Estrogens have been convincingly shown to be highly effective in preventing and reversing menopause-related conditions, such as hot flushes, urogenital complaints, and postmenopausal bone loss. Observational studies report that long-term, estrogen-containing, postmenopausal hormone replacement therapy (HRT) leads to a substantial reduction in hip fractures, myocardial infarction, and possibly colonic cancer, with important consequences for health and quality of life. Estrogen replacement may postpone the onset of Alzheimer's disease and extend life. While many of these effects are biologically plausible, with a variety of cellular mechanisms being involved, only ongoing and future large-scale randomized clinical trials can and should define the effects of HRT more precisely. Long-term compliance is a key issue for long-term benefits, and offering women a choice of administration routes and regimens can only be beneficial in this respect. Pills, patches, gels, and implants are all widely prescribed. Intravaginal or intranasal forms of administration, which are very easy to use and adaptable on an individual level, are among the new options which could improve long-term continuation of HRT use. Fear of breast cancer and recurrence of vaginal bleeding are real concerns for many women considering HRT. This has led to research into lower-dose, estrogen-containing regimens, into continuous combined regimens, and into the potential of estrogen receptor alpha or beta binding molecules that may help to prevent such problems from arising. The prospects for safe and effective postmenopausal HRT with either estrogens or estrogen-like drugs are very promising when these drugs are used in a patient-tailored, risk profile-based manner.

Estrogen Replacement Therapy↗
PubMed2001

Effects of 15 months of 17 beta-estradiol and dydrogesterone on systolic cardiac function according to quantitative and Doppler echocardiography in healthy postmenopausal women.

OBJECTIVE: Our goal was to investigate the short-term and intermediate effects of low-dose hormone replacement therapy on echocardiographic parameters of cardiac function in healthy postmenopausal women. STUDY DESIGN: In a prospective, controlled study 30 healthy postmenopausal women (mean age, 52 +/- 3 years) were randomly assigned to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17 beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and thereafter 2 mg 17 beta-estradiol combined with 10 mg dydrogesterone for a period of 3 months. The control group (n = 15) received no treatment. M-mode, quantitative 2-dimensional, and Doppler echocardiographic measurements were performed at baseline and within the 17 beta-estradiol phase at 3, 12, and 15 months. RESULTS: After 12 months significant differences in change between the 2 groups were found for left ventricular end-diastolic and left ventricular end-systolic diameters, left ventricular mass index, and stroke volume index. These differences were caused by changes in the control group rather than in the hormone replacement therapy group, in which no significant within-group changes were found. All other parameters measured showed no effect. CONCLUSION: Within 15 months of 17 beta-estradiol and dydrogesterone treatment no clinically relevant differences were found in the M-mode, quantitative 2-dimensional, and Doppler echocardiographic parameters measured in this study. It is suggested that 15 months of treatment probably is too short a period for detection of direct effects on the heart itself.

Double-Blind Method↗