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Biomedical subjects

F M Helmerhorst

Publications and source records attributed to F M Helmerhorst.

At least 37 records · Page 2Linked to original sources
PubMed2004

Preeclampsia and its interaction with common variants in thrombophilia genes.

Recently, it has been proposed that abnormalities in coagulation and fibrinolysis contribute to the development of preeclampsia by increasing the thrombotic tendency. This hypothesis was tested in women who have had preeclampsia (cases) compared with matched controls. Polymorphisms in the thrombophilia genes [plasminogen activator inhibitor type 1 [PAI-1 -675(4G/5G)], thrombin activatable fibrinolysis inhibitor (TAFI -438G/A and 1040C/T), methylenetetrahydrofolate reductase (MTHFR 677C/T), factor V (FV Leiden R/Q506), prothrombin (FII 20210G/A) and factor XIIIA (FXIIIA V/L34)] were determined in 157 women with preeclampsia and 157 women with uncomplicated pregnancy. The associated risk of preeclampsia was analyzed using logistic regression methods. The frequency distributions of the genotypes of these six polymorphisms in thrombophilia genes were similar in the case and control groups. We found no differences in the prevalence of genetic risk factors of thrombosis in women with preeclampsia compared with controls, which makes it unlikely that these polymorphisms are risk factors for preeclampsia.

Adult↗
PubMed2004

Miscarriage but not fecundity is associated with progression of joint destruction in rheumatoid arthritis.

OBJECTIVE: To determine whether reproductive history before disease onset is associated with severity of joint destruction in rheumatoid arthritis. METHODS: A special early arthritis clinic (EAC) was established at the department of rheumatology of Leiden University Medical Centre. General practitioners were encouraged to refer patients with joint complaints to this clinic, where the diagnosis of rheumatoid arthritis was made by a rheumatologist. In all, 113 female patients with definite rheumatoid arthritis were included in this study. A structured questionnaire was administered and joint damage was assessed by sequential x rays of the hands and feet, using the modified Sharp score. RESULTS: The length of time of unprotected intercourse until first pregnancy (fecundity) was comparable with data from earlier studies, with 16% of the patients reporting a time to first pregnancy of more than 12 months. Fecundity did not reflect the extent of joint damage over time. The miscarriage rate was 15% per pregnancy, comparable to population figures (12-15%). A significant increase in joint damage over a two year follow up was found in patients with rheumatoid arthritis who had experienced at least one miscarriage compared with those who had never had a miscarriage (mean modified Sharp scores at 2 years, 24 (95% confidence interval, 15 to 32) and 16 (10 to 23), respectively; p<0.05). At baseline, the Sharp scores were similar in the two subgroups. CONCLUSIONS: Miscarriage before disease onset but not fecundity is associated with the progression of joint damage in rheumatoid arthritis.

Abortion, Spontaneous↗
PubMed2003

[Breast cancer and the use of the hormones around the menopause].

Following the publication of the 'Million women study', commotion has broken out in the media about the relationship between hormone use around the menopause and breast cancer. In this study, women were asked about possible risk factors for breast cancer, including hormone replacement therapy, prior to breast cancer screening. After an average follow-up period of 2.6 years, it was found that breast cancer more frequently occurred among women who had recently used an oestrogen-progestagen preparation (relative risk (RR): 2.00; 95%-CI: 1.88-2.12), an oestrogen preparation (RR: 1.30; 1.21-1.40) or tibolone (RR: 1.45; 1.25-1.68) than among women who had not used either of these. Methodologically, the study contains both strengths and weaknesses. However, the findings agree with those from an earlier randomised study. Current users of hormone use were more likely than never users to die from breast cancer (RR: 1.22; 1.00-1.48). For the prescription of hormone replacement therapy, the twice as high relative risk of breast cancer together with the other potentially life-threatening side effects of hormone replacement therapy need to be weighed up against the complaints which form the indication for the prescription. Therefore, the advice for hormone replacement therapy continues to be that it should, if necessary, be made available as a treatment option for a short period (3 months) and only in the case of serious and debilitating complaints. Long-term preventative use, as happens in practice, is not indicated due to the risk of relatively serious side effects.

Breast Neoplasms↗
PubMed2003

Combination contraceptives: effects on weight.

BACKGROUND: Weight gain is often attributed as a side effect of combination hormonal contraceptive, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. Nevertheless, a causal relationship between combination contraceptives and weight gain has not been established. OBJECTIVES: The aim of the review was to evaluate the association between combination contraceptive use and changes in weight. SEARCH STRATEGY: We searched the computerized databases MEDLINE, Popline, CENTRAL, EMBASE, and LILACS for studies of combination contraceptives. We also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. SELECTION CRITERIA: All English-language, randomized controlled trials at least three treatment cycles in duration that compared a combination contraceptive to a placebo or with a combination contraceptive that differed in drug, dosage, regimen, and/or study length were eligible. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan 4.1, and a second reviewer verified the data entered. Depending on the data available, the weighted mean difference using a fixed effects model with 95% confidence intervals was calculated for the mean change in weight between baseline and post-treatment measurements or the Peto odds ratio with 95% confidence intervals was calculated using the proportion of women who gained or lost more than a specified amount of weight. MAIN RESULTS: The three placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups where this was studied. REVIEWER'S CONCLUSIONS: Available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.

Body Weight↗
PubMed2003

The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women.

With regard to oral contraceptives, much research has concentrated on venous thrombosis and on the coronary and cerebral forms of atherosclerotic disease, while peripheral arterial disease (PAD) has received little attention. In this case-control study, we assessed oral contraceptive use and the risk of PAD in young women using a population-based case-control study. The women were 18-49 years of age, and had been admitted to a collaborating hospital between January 1990 and October 1995, and had a diagnosis of PAD. Participants were patients with PAD (n = 152), and control women (n = 925), identified by random digit dialing. The diagnosis of PAD was based almost exclusively on intra-arterial angiography. Patients and control subjects filled out the same structured questionnaire, which included questions on medical history, cardiovascular risk factors, and contraceptive use. The adjusted odds ratio for PAD in women using any type of oral contraceptives vs. no use, was 3.8 (95% CI 2.4-5.8). When first generation oral contraceptive use was compared with no use, the odds ratio was 8.7 (95% CI 3.6-21.3). For second and third generation oral contraceptives, the adjusted odds ratios (compared with non-users) were 2.6 (95% CI 1.4-4.9) and 3.0 (95% CI 1.4-6.6), respectively. This is the first study on oral contraceptive use and PAD in humans. All types of oral contraceptives were associated with an increased risk of PAD.

Adult↗
PubMed2003

Estrogens, progestogens and thrombosis.

Hundreds of millions of women worldwide use either oral contraceptives or postmenopausal hormone replacement. The use of oral contraceptives leads to an increased risk of venous thrombosis, of myocardial infarction, of stroke and of peripheral artery disease, the risks of which are highest during the first year of use. Women with coagulation abnormalities have a higher risk of venous thrombosis when they use oral contraceptives (or postmenopausal hormones) than women without these abnormalities. The risk of venous thrombosis is also higher for preparations containing desogestrel or gestodene (third-generation progestogens) than for those containing levonorgestrel (second-generation progestogens). A previous thrombosis as well as obesity also increase the risk of oral contraceptive-related thrombosis. Hormone replacement therapy increases the risk of venous thrombosis, and has no beneficial, and possibly even a detrimental, effect on the risk of arterial disease. The risk of arterial disease in oral contraceptive users and users of hormone replacement therapy is at most weakly affected by the presence of prothrombotic abnormalities.

Contraceptives, Oral↗
PubMed2002

Estrogen reduces vascular endothelial growth factor(164) expression in the mouse nucleus paraventricularis of the hypothalamus.

The aim of the present study was to establish whether estrogen and corticosteroids exert effects on vascular endothelial growth factor (VEGF)(164) expression in the hippocampus and nucleus paraventricularis of the hypothalamus by in situ hybridization. Female mice were ovariectomized and treated either with estradiol benzoate or vehicle and male mice were either adrenalectomized or sham-operated. Ovariectomy plus estrogen reduced VEGF(164) expression in the nucleus paraventricularis but not in the hippocampus. Adrenalectomy did not influence VEGF(164) mRNA levels in the hippocampus and nucleus paraventricularis. Our results show for the first time an inhibitory effect of estrogen on VEGF(164) expression in the nucleus paraventricularis and suggest a role for estrogen in the regulation of VEGF(164) expression and function in the central nervous system.

Adrenalectomy↗
PubMed2002

[Adverse cardiovascular effects of postmenopausal hormone replacement therapy].

The views on the effects of postmenopausal hormone-replacement therapy (HRT) on cardiovascular disease have moved from one end of the spectrum to the other over the past decades. The presumed beneficial effects of HRT on arterial cardiovascular disease were based on observational findings and have led to the widespread use of these agents. However, recent large-scale randomised, placebo-controlled trials have demonstrated that HRT in women with a history of arterial diseases initially increases the risk of recurrent disease, while offering no benefit in the long term. Healthy postmenopausal women on HRT have an increased risk of arterial cardiovascular events compared with those taking placebo (relative risk 1.29; 95% CI: 1.02-1.63). Finally, the risk of venous thrombosis and pulmonary embolism is increased with the use of HRT. These results demonstrate that bias and confounding can play an important role in observational research and underscore the importance of randomised, placebo-controlled trials when studying the efficacy of drugs.

Cardiovascular Diseases↗
PubMed2002

Female hormones and thrombosis.

Exogenous hormones are used by more than a hundred million women worldwide as oral contraceptives or for postmenopausal hormone replacement. Oral contraceptives increase the risk of venous thrombosis, of myocardial infarction, and of stroke. The risk is highest during the first year of use. The venous thrombotic risk of oral contraceptives is high among women with coagulation abnormalities and with so-called third-generation contraceptives (containing desogestrel or gestodene). The risk of myocardial infarction does not appear to depend on coagulation abnormalities or the type of oral contraceptive. Hormone replacement therapy increases the risk of venous thrombosis. This risk is also highest in the first year of use and among women with coagulation abnormalities. The risk becomes very high in women with a previous venous thrombosis. Randomized trials have not confirmed a beneficial effect of postmenopausal hormones on the occurrence of myocardial infarction.

Contraceptives, Oral, Hormonal↗
PubMed2002

Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment.

The effects of two third-generation monophasic combined oral contraceptives (COC) and a postmenopausal hormone replacement therapy (HRT) consisting of 2 mg 17 beta-oestradiol on the plasma level of the acute-phase indicator C-reactive protein (CRP) and other acute-phase reactants were analysed. Two studies were conducted: (1) a randomised, open-label study with two different oral contraceptive preparations with an equal dose of ethinylestradiol (30 micrograms) and a different progestogen, either 75 micrograms gestodene (GSD-EE) or 150 micrograms desogestrel (DSG-EE); blood samples of 39 young women were analysed before and after 3, 6, 12 treatment cycles; (2) a randomised, blinded placebo-controlled study with 2 mg 17 beta-oestradiol in postmenopausal women with non-insulin-dependent diabetes mellitus without signs of cardiac involvement; blood samples of 38 women were analysed before and after 6 weeks of treatment. The plasma concentration of CRP increased strongly during oral contraceptive use for both preparations; the increase persisted over 12 cycles. The already elevated CRP in postmenopausal diabetic women showed a moderate increase after 6 weeks of treatment with 17 beta-oestradiol. CRP increases during oral contraceptive use were associated with changes in some other acute-phase proteins (fibrinogen, ceruloplasmin, von Willebrand factor [vWF]) originating from the liver and vessel wall, but not in others (interleukin-6 [IL-6], serum amyloid A [SAA]). The results demonstrate an increase in a specific set of acute-phase reactants caused by oestrogen-containing preparations. It is proposed that the pro-inflammatory effect of oestrogens should be checked for a relationship with the increased risk of thromboembolism for both oral contraceptive and HRT.

Adult↗
PubMed2002

Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis.

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 77 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7-8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable.

Case-Control Studies↗
PubMed2002

Gonadotrophin stimulation reduces VEGF(120) expression in the mouse uterus during the peri-implantation period.

BACKGROUND: Ovarian stimulation by gonadotrophin treatment exerts negative effects on implantation and embryonic development. We investigated whether gonadotrophin treatment affects VEGF(120) mRNA expression during the peri-implantation period. METHODS: Two groups of adult female CD1 mice were used: the hormone-treated group was injected i.p. with urinary human FSH (5 IU in 0.1 ml saline) and urinary HCG (5 IU in 0.1 ml saline). Spontaneously ovulating mice served as controls and received saline injections. The pregnant mice were killed on embryonic development (ED) days 0, 3, 4, 5 and 6 (day of vaginal plug detection is considered as ED0). The uteri with the implanted embryos were processed for in-situ hybridization for VEGF(120). A separate group of control and hormone-treated pregnant mice were allowed to give birth. Litter size, birthweight and length of gestational period were noted. RESULTS: Gonadotrophin treatment decreased VEGF(120) mRNA levels, delayed implantation, reduced the size of the embryo implantation site on ED5 and ED6 and prolonged the gestational period. CONCLUSIONS: Gonadotrophin treatment reduces VEGF(120) expression which may have serious consequences for normal embryonic development. The present data cannot establish whether this effect is a cause or consequence of delayed implantation.

Alternative Splicing↗
PubMed2001

Oral contraceptives and the risk of myocardial infarction.

BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.

Adolescent↗
PubMed2001

Biphasic versus monophasic oral contraceptives for contraception.

OBJECTIVES: To compare biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic oral contraceptives are less effective in preventing pregnancy than are monophasic oral contraceptives, and (b) biphasic oral contraceptives cause more side effects, give poorer cycle control, and have lower continuation rates. SEARCH STRATEGY: We searched computerized databases MEDLINE, EMBASE, Popline and the Cochrane Controlled Trial Register. Additionally we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the U.S. SELECTION CRITERIA: We included randomized controlled trials comparing any biphasic oral contraceptive with any monophasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplemental information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding, and study discontinuation due to intermenstrual bleeding. MAIN RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. Percival-Smith et al. (1990) examined 533 user cycles of a biphasic pill (norethindrone 500 mcg/ethinyl estradiol 35 mcg for ten days, followed by norethindrone 1000 mcg/ethinyl estradiol 35 mcg for eleven days; Ortho 10/11) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 mcg/ethinyl estradiol 30 mcg daily; Loestrin). The study found no significant differences in intermenstrual bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. REVIEWER'S CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Contraception↗
PubMed2001

Biphasic versus triphasic oral contraceptives for contraception.

BACKGROUND: Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic oral contraceptive pills as compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage. OBJECTIVES: To compare biphasic oral contraceptives with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched computerized databases MEDLINE, EMBASE, POPLINE and the Cochrane Controlled Trial Register. Additionally we searched the reference lists of potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the U.S. SELECTION CRITERIA: We included randomized controlled trial comparing any biphasic oral contraceptive with any triphasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplemental information about the study methods and outcomes. We entered the data in RevMan 3.1 and later imported them into RevMan 4.1. We calculated Peto odds ratios for incidence of incidence of discontinuation due to medical reasons, intermenstrual bleeding, absence of withdrawal bleeding, and discontinuation due to intermenstrual bleeding. MAIN RESULTS: Only two trials of limited quality met our inclusion criteria. Larranaga (1978) compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival Smith (1990) compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95%CI 1.3-2.2) for the biphasic pill compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95%CI 3.1-13). In contrast, cycle control with the biphasic pill was comparable to that with the triphasic pill containing the same progestin (norethindrone). REVIEWER'S CONCLUSIONS: The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given the high losses to follow-up after randomization, these reports may be better considered observational in nature. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important that the phasic regimen in determining bleeding patterns.

Contraception↗
PubMed2001

Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinyl estradiol on the human endometrium.

OBJECTIVE: To provide an in-depth assessment of the effects of the combined oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (Yasmin, Schering AG, Berlin) on the endometrium by means of endometrial morphometry in comparison to an untreated cycle. DESIGN: The open, multicenter study consisted of one untreated precycle and 13 treatment cycles. SETTING: Four gynecologic clinics in Belgium, The Netherlands, and Switzerland were involved. PATIENT(S): Forty women with a history of regular menstrual cycles. INTERVENTION(S): Before the commencement of the trial, 3 months without any hormonal intake was obligatory. The first endometrial sample was done in the untreated precycle, adjusted to the day of LH peak plus 5 to 6 days. During the medication phase, endometrial samples were taken at cycle 3, 6 and 13. MAIN OUTCOME MEASURE(S): Primary outcome measure of the study was the morphologic assessment of the endometrium with measures such as glandular diameter, glandular epithelial height, and number of vacuolated cells per 1,000 glandular cells. Furthermore, the endometrial thickness was measured by ultrasound. RESULT(S): After 13 cycles of medication use the endometrium had an atrophic appearance in 63% of the subjects. The size of the glands, the glandular epithelial height, and the number of glands per square millimeter were already significantly reduced after 3 months' use. Histological and ultrasonographical evaluation of the endometrium indicated a suppression of the proliferative activity of the endometrium. CONCLUSION(S): The combination of 30 microg of ethinyl estradiol with 3 mg of drospirenone induces changes of the endometrium that are comparable with other combined oral contraceptives and exhibits a marked antiproliferative effect on the endometrium. The medication was proven to be an effective oral contraceptive and revealed good cycle control characteristics.

Adult↗