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Biomedical subjects

O Lidegaard

Publications and source records attributed to O Lidegaard.

At least 19 recordsLinked to original sources
PubMed2000

[Severe male infertility. Genetic investigation and counseling prior to intracytoplasmic sperm injections].

Intracytoplasmatic sperm injection (ICSI) has improved the success rate in treating severe male infertility. The method may now be used with sperm from the epididymis and testis. This article summarizes our knowledge on genetic factors affecting male gamete formation or function. Infertile men with severe impairment of spermatogenesis showed a higher than normal incidence of chromosomal abnormalities and 10-20% had microdeletion, in the Y-chromosome. About 75% of males with congenital bilateral absence of vas deferens (CBAVD) have mutations in the cystic fibrosis trans-membrane conductance regulator (CFTR) gene. In conclusion, we recommend genetic counselling to all couples with a diagnosis of male infertility prior to ICSI. Men with severe oligozoospermia or non-obstructive azoospermia should have karyotype analysis performed and with establishment of diagnostic tools to reveal Y-chromosome deletions, this should be offered to the same group of men. Men with obstructive azoospermia and congenital albilateral absence of vas deferens as well as their wives should be screened for cystic fibrosis mutations.

Chromosome Aberrations↗
PubMed2000

Risk factors among young women with endometrial cancer: a Danish case-control study.

OBJECTIVE: This study was undertaken to identify and quantify risk factors for endometrial cancer among young women. STUDY DESIGN: This case-control study included all Danish women <50 years old who had endometrial cancer diagnosed during the period 1987 to 1994. A total of 237 case patients and 538 population control subjects matched with the case patients for age and residence were included in the analysis. RESULTS: Women with a family history of endometrial cancer had an odds ratio for endometrial cancer of 2.1 (95% confidence interval, 1.1-3.8)). Completion of 1 term pregnancy implied an odds ratio of 0.6 (95% confidence interval, 0.3-1.1). The risk of endometrial cancer decreased significantly with increasing age at first birth and with the number of induced abortions. Use of oral contraceptives for 1 to 5 years decreased the risk of endometrial cancer (odds ratio, 0.2; 95% confidence interval, 0.1-0.3). The odds ratio for endometrial cancer among women who received hormone replacement therapy for 1 to 5 years was 3.1 (95% confidence interval, 1.4-7.0). Body mass index was not demonstrated to be an independent risk factor in this study. The protective impacts of the different exposures (risk factors) can be expressed as etiologic fractions, which indicate how much each exposure reduces the occurrence of endometrial cancer compared with a situation without the existence of that particular exposure. These fractions were as follows: oral contraceptive use for > or =1 year, -45%; 2 term pregnancies, -88%; age > or =30 y when giving birth for the first time, -38%; and a history of incomplete pregnancy, -16%. CONCLUSION: A number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women: family history, reproductive history, hormone replacement therapy, and the use of oral contraceptives. Among young women reproductive variables imply the greatest prophylactic potential.

Abortion, Induced↗
PubMed2000

Occlusive vascular diseases in oral contraceptive users. Epidemiology, pathology and mechanisms.

Despite being an unprecedented departure from normal physiology, the combined oral contraceptive is not only highly effective, but it also has a remarkably good safety record. Concerns over safety persist, though, particularly with regard to venous thromboembolism (VTE), stroke and myocardial infarction (MI). Epidemiological studies consistently show an increase in risk of VTE, but the results are more contentious with regard to arterial diseases. Despite 40 years of research, the mechanisms behind these adverse effects are not understood. In this review, we integrate information from published studies of the epidemiology and pathology of the occlusive vascular diseases and their risk factors to identify likely explanations for pathogenesis in oral contraceptive users. Oral contraceptives induce both prothrombotic and fibrinolytic changes in haemostatic factors and an imbalance in haemostasis is likely to be important in oral contraceptive-induced VTE. The complexity of the changes involved and the difficulty of ascribing clinical significance has meant that uncertainty persists. A seriously under-researched area concerns vascular changes in oral contraceptive users. Histologically, endothelial and intimal proliferation have been identified in women exposed to high plasma estrogen concentrations and these lesions are associated with thrombotic occlusion. Other structural changes may result in increased vascular permeability, loss of vascular tone and venous stasis. With regard to arterial disease risk, epidemiological information relating to dose effects and joint effects with other risk factors, and studies of pathology and changes in risk factors, suggests that oral contraceptive use per se does not cause arterial disease. It can, nevertheless, synergise very powerfully with subclinical endothelial damage to promote arterial occlusion. Accordingly, the prothrombotic effects of the oral contraceptive estrogen intervene in a cycle of endothelial damage and repair which would otherwise remain clinically silent or would ultimately progress - in, for example, the presence of cigarette smoking or hypertension - to atherosclerosis. Future work in this area should focus on modification of the effects of established risk factors by oral contraceptive use rather than modification of the supposed risk of oral contraceptive use by established risk factors. Attempts to understand vascular occlusion in oral contraceptive users in terms of the general features of VTE or with reference to atherosclerosis may be limiting, and future work needs to acknowledge that such occlusions may have unique features. Unequivocal identification of the mechanisms involved would contribute considerably to the alleviation of fears over vascular disease and to the development of even safer formulations.

Adult↗
PubMed1999

[Early medical abortion. An update].

Early medical abortion was introduced in Denmark in 1998. In countries in which this practice has been in use for several years, clinical studies have identified an effective and at the same time gentle regimen. For the time being, this regimen is a combination of the antiprogestogen "mifepristone" and a prostaglandin E1 analogue. Among women with pregnancies up to eight weeks of gestation, 95% will have a complete abortion on a regimen of 600 mg oral mifepristone combined 24 hours later with 1 mg vaginal gemeprost. About five percent will undergo evacuation due to incomplete abortion or heavy bleeding. Although many women experience moderate or severe pain, nausea or vomiting, the tolerability is generally good. Complications wuch as infection or excessive bleeding occur in less than one percent. It is concluded that medical abortion is a good alternative to surgical abortion, and that women who wish an abortion have to be referred to hospital as early as possible in order not to pass the time limit of medical abortion.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

[The first 100 early medical abortions].

Early medical abortion was introduced in Denmark in 1998. This article describes our experiences with the first 100 patients at Herlev University Hospital. The regimen was 600 mg mifepriston (RU486) given orally on day one. All women had an ultrasound examination before RU486 was given in order to ensure an intrauterine pregnancy and a gestationel age of eight weeks or less, and all had a quantitative P-hCG. On day three the patients received 1 mg gemeprost as vagitory as well as a paracetamol/-codein suppository. They were observed in the department for four hours, and were thereafter discharged no matter whether a complete abortion had occurred ot not. On day 14 a new P-hCG was taken. All women in whom the hCG value was not reduced to one half of the initial value or less underwent a new ultrasound examination. All women were given a questionnaire. The effectivity was 96%. Four of 100 women were evacuated: one due to severe vaginal bleeding four hours after application of gemeprost, two because of womiting soon after having taken RU486 and one due to incomplete abortion. Half of the women began to bleed before application of gemeprost, and 91% had bleeding for more than six days. One half had no side effects to mifepristone, the other half had mild nausea. Nine of ten patients were sufficiently relieved of pain without opioids, whereas 10% were insufficiently pain relieved. Eight of ten patients would choose the same method again, in case of a future need for an induced abortion. The reason for not preferring a medical abortion among the remaining 20% was primarily pain. Early medical abortion should be offered to all women referred for induced abortion with a gestational age of eight weeks or less.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Smoking and use of oral contraceptives: impact on thrombotic diseases.

OBJECTIVES: The study was intended to evaluate the effects of oral contraceptives and smoking on the risks of arterial and venous thromboembolic diseases among young women. STUDY DESIGN: The study included a survey of data from published epidemiologic studies and evaluation of registry records of all Danish women discharged from the hospital from 1980 through 1993 after a first thromboembolic event. Questionnaires returned by survivors of such events and by control women during the period from 1994 through 1995 were analyzed. RESULTS: In the 1980-1993 data the absolute risk of thrombotic diseases was seen to increase rapidly with age-exponentially for acute myocardial infarction or cerebral thromboembolic attack, linearly for venous thromboembolism-with risks of arterial diseases exceeding those of venous diseases. In the 1994-1995 data the relative risk of thrombotic diseases was seen to increase among users of oral contraceptives irrespective of age. Risk of venous thromboembolism (but not of acute myocardial infarction or cerebral thromboembolic attack) declined as duration of current oral contraceptive use lengthened, risk of acute myocardial infarction or cerebral thromboembolic attack was significantly decreased as ethinyl estradiol doses were reduced, and the relative risk (compared with nonusers of oral contraceptives) for arterial thromboembolic disease among users of desogestrel or gestodene (in conjunction with midrange or low doses of ethinyl estradiol) was lower than the relative risk among users of second-generation progestogens (in conjunction with midrange doses of ethinyl estradiol). The combination of smoking with oral contraceptive use may have a synergistic effect on risks of acute myocardial infarction and cerebral thromboembolic attack (but not of venous thromboembolism), particularly among users of high-dose (50 micrograms) ethinyl estradiol preparations. CONCLUSION: Among the formulations currently marketed in Denmark, where only the progestins desogestrel and gestodene are available with low-dose (20 micrograms) ethinyl estradiol (and only desogestrel was available in that form at the time of our studies), we prefer these third-generation oral contraceptives for smokers. We might also consider such oral contraceptives for women >35 years old as long as they had no other risk factors for thrombotic arterial diseases.

Adolescent↗
PubMed1999

Oral contraceptives and thrombosis. From risk estimates to health impact.

OBJECTIVE: The scientific debate on oral contraceptives (OCs) and thrombotic diseases continues unabated. The aim of this survey was to evaluate available scientific data on OCs and thrombotic diseases and to make tentative prescription recommendations of OCs to women with and without various thrombotic risk factors. CONSENSUS: In women 15-29 years old, venous thromboembolism is about twice as common as arterial complications. In women between 30 and 44 years, the number of arterial complications exceeds venous diseases by about 50%. The mortality from arterial diseases is 3.5 times higher than the number of deaths from venous diseases in women below 30 years, and 8.5 times higher in women 30-44 years old. A significant disability is more frequent in women suffering and surviving an arterial complication than in women with venous thromboembolism. Although many important scientific issues still have to be addressed, the available scientific data suggests a differential influence of OCs with second and third generation progestagens on the risk of venous and arterial diseases. OCs with second generation progestagens seem to confer a smaller increase in the risk of venous diseases and a higher increase in risk of arterial complications, compared with OCs containing third generation progestagens. The possible difference on the venous side seems to be smaller than primarily anticipated. RESULTS: Young women without any known risk factor for thrombotic diseases may use any low-dose OC. If OCs are prescribed to women with known risk factors for arterial thrombotic disease; e.g. smoking, diabetes, controlled hypertension, migraine without aura, family disposition of acute myocardial infarction (AMI) or thrombotic stroke, a low-dose pill with a third generation progestagen may have an advantage. If OCs are considered for women with risk factors for venous disease such as severe obesity, varicose veins, family history of VTE or with factor V Leiden mutation, a low-dose combined pill with a second generation progestagen may be preferable. In women above 30 years, OCs with third generation progestagens generally seem to confer less overall thrombotic morbidity, mortality and disability than OCs with second generation progestagens. These women should reconsider, however, the indication of combined OCs in the presence of significant risk factors of thrombotic diseases.

Adolescent↗
PubMed1998

[Estrogen replacement in women treated for breast cancer].

Oestrogen replacement therapy in women with a history of breast cancer has long been considered contraindicated. However, the literature does not indicate an increased risk of recurrent breast cancer in postmenopausal women receiving oestrogen replacement therapy. We advocate that women with a history of breast cancer without nodal involvement could be offered oestrogen replacement therapy and thereby benefit from prevention of cardiovascular disease and osteoporosis. But the patients must accept a potentially increased risk of recurrence. We emphasize the need for randomized prospective studies.

Breast Neoplasms↗
PubMed1998

Cerebral thrombosis and oral contraceptives. A case-control study.

To assess the influence of oral contraceptives (OC) on the risk of cerebral thrombosis and transient cerebral ischemic attacks, a 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old who suffered a cerebral thromboembolic attack (CTA) during the period 1994-95 and 1200 age matched control subjects were included. Of 309 patients and 1200 control subjects questionnaires sent out, 271 patients (87.7%) and 1074 control subjects (89.5%) responded and agreed to participate. After exclusion of women with nonvalid diagnoses, previous thromboembolic diseases, or current pregnancy, 219 patients and 1041 control subjects were available for analysis. After confounder control and with nonusers as reference, current users of first generation OC (50 micrograms of ethinyl estradiol [EE] or estrans) had an odds ratio (OR) of CTA of 1.86 (95% confidence interval [CI] 0.88-3.92); users of second generation OC (levonorgestrel or norgestimate) had an OR of 2.37 (1.35-4.16); and users of third generation OC (desogestrel or gestodene) had an OR of 1.32 (0.78-2.22). Users of OC with 50, 30-40, or 20 micrograms EE had OR of 2.65 (1.11-6.34), 1.60 (1.05-2.43), and 1.59 (0.57-4.58), respectively. Odds ratios for specific progestin types were as follows: estrans 1.37 (0.60-3.13), levonorgestrel 2.43 (1.40-4.21), norgestimate 7.09 (1.87-26.8), desogestrel 1.62 (0.72-3.63), and gestodene 1.24 (0.67-2.30). Duration of use was without significant influence on the risk and the OR were constant across the age bands. Compared with women who had never used OC, former users had an OR of CTA of 0.95 (0.66-1.51). In conclusion, use of OC with 50 micrograms of EE and OC with second generation progestins increased the risk of CTA significantly. OC with third generation progestins did not have any significant influence on the risk of CTA. The risk of CTA among former users of OC was not increased.

Adolescent↗
PubMed1998

Oral contraceptives and venous thromboembolism. A case-control study.

To assess the influence of oral contraceptives (OC) on the risk for venous thromboembolism (VTE) in young women, a 5-year case-control study including all women 15-44 years old suffering a first deep venous thrombosis or a first pulmonary embolism from all Danish hospitals, along with 1200 control subjects during the period 1994-1995, was conducted. Of 586 patient and 1200 control subject questionnaires sent out, 523 patient (89.2%) and 1074 control (89.5%) questionnaires were returned with an agreement to participate. After exclusion of women with nonvalid diagnoses, women who were pregnant, and women with previous VTE or acute myocardial infarction (AMI), 375 patients and 1041 control subjects were available for analysis. Potential tested confounders included: body mass index, length of OC use, family history of VTE, AMI, or stroke, smoking habits, coagulopathies, diabetes, years of schooling, certainty of diagnosis, previous births, and treated hypertension during any pregnancy. A multivariate analysis was performed. Estrogen dose had no influence on the risk for VTE. The risk for VTE among current users of OC was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: < 1 year; 5.1 (3.1-8.5); 1-5 years; 2.5 (1.6-4.1); and > 5 years; 2.1 (1.5-3.1), all compared with those for nonusers of OC. This trend was still significant after adjustment for progestin types. Without adjustment for duration of use, current users of OC with second generation (levonorgestrel or norgestimate) and third generation (desogestrel or gestodene) progestins had OR of 1.8 (1.1-2.9) and 3.2 (2.3-4.4), respectively. After correction for duration of use, however, no significant differences were found between users of OC with different types of progestins. In conclusion, OC increase the risk for VTE significantly. The risk among current users of OC is primarily influenced by duration of use. No difference in risk was found according to estrogen dose, and the difference in risk between different types of progestins was not statistically significant after adjustment for duration of use.

Adolescent↗
PubMed1998

Ovarian stimulation and borderline ovarian tumors: a case-control study.

OBJECTIVE: To assess the risk of borderline ovarian cancer among infertile women treated with fertility drugs. DESIGN: Case-control study. SETTING: Nationwide data obtained from public registers and postal questionnaires. PATIENT(S): All Danish women <60 years old with borderline ovarian cancer during the period 1989-1994 and randomly selected population controls. The analysis included 231 cases and 1,721 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Influence of parity, infertility, and fertility drugs on the risk of borderline ovarian cancer after multivariate confounder control. RESULT(S): The odds ratio (OR) for borderline ovarian cancer among infertile untreated nulliparous women compared with fertile nulliparous women was 1.9. The OR for borderline ovarian cancer among treated nulliparous women compared with untreated infertile nulliparous women was 1.5, and the OR among treated parous women compared with untreated infertile parous women was 1.5. CONCLUSION(S): Among fertile women, the difference in the risk of borderline ovarian cancer between nulliparous women and parous women was not statistically significant. Nulliparous women who were infertile and who did not receive medical treatment had a twofold higher risk of borderline ovarian cancer than fertile nulliparous women. There was no statistically significant increase in the risk of borderline ovarian cancer among nulliparous women who were treated with fertility drugs compared with nulliparous untreated infertile women or among parous women who were treated with fertility drugs compared with parous untreated infertile women.

Adult↗
PubMed1998

Thrombotic diseases in young women and the influence of oral contraceptives.

OBJECTIVE: In the evaluation of the clinical impact of thrombotic diseases in young women, age-specific incidence rates must be calculated for both arterial and venous thrombotic diseases, but also the case-fatality rate and figures for the clinical consequences among those who survive thrombosis must be included. The aim of this analysis was to quantify the clinical impacts of both arterial and venous thrombotic diseases among young, nonpregnant women and thereafter to assess the influences of oral contraceptives on these measures. STUDY DESIGN: Nationwide register data on the morbidity and mortality of venous thromboembolism, myocardial infarction, and thrombotic stroke in Denmark, 1980-1993, and 3 ongoing case-control studies to assess the influence of oral contraceptives on the risk for development of these thrombotic diseases. RESULTS: In women 15-29 years old venous thromboembolism is about twice as common as arterial complications, whereas in women 30-44 years old the number of arterial complications exceeds that of venous diseases by about 50%. The mortality rate from arterial diseases is 3.5 times higher than that from venous diseases among women <30 years old and 8.5 times higher than that from venous diseases in women 30-44 years old. The proportion of women with a significant disability among women who had an arterial complication was about 30%; the proportion was about 5% among women with venous thromboembolism. CONCLUSION: Anticipating a differential influence on venous and arterial diseases from oral contraceptives with second- and third-generation progestogens, it was calculated that users of oral contraceptives with second-generation progestogens had 30% greater increased risk of thrombotic diseases, 260% greater increased risk of thrombotic deaths, and 220% greater increased risk of thrombotic disability than users of oral contraceptives with third-generation progestogens.

Adolescent↗
PubMed1998

[P-pills and thrombosis].

This review provides an account of the present situation as reflected by findings in recent studies, which illustrate epidemiological, clinical and metabolic aspects of thrombosis associated with oral contraceptive (OC) usage. With the reduction of the oestrogen content of OCs, the relative risk for acute myocardial or cerebral thrombosis is now 1.5-3. Low-dose OCs containing third generation gestagens seem to be associated with less risk of infarction, and possibly of cerebral thrombosis, than are OCs containing second generation gestagens. The risk of venous thrombosis is increased 2-4-fold in conjunction with the usage of low-dose OCs with second generation gestagens, and possibly slightly more (3-5-fold) in conjunction with OCs containing third generation gestagens, though this is of small clinical significance. When prescribing OCs for women at an increased risk of venous thrombosis, a low-dose pill with a second generation progestagen seems to be preferable. If OCs are prescribed to women at an increased risk of arterial thrombosis, OCs with third generation progestagens seem to be a reasonable first choice. Women with no thrombotic predisposion can safely use any type of low-dose OCs [corrected].

Contraceptives, Oral, Hormonal↗
PubMed1997

Hormone replacement therapy and risk of non-fatal stroke.

BACKGROUND: The effect of postmenopausal hormone replacement therapy (HRT) on the risk of subtypes of stroke is as yet unclear. To investigate the effect of oestrogen and combined oestrogen-progestagen therapy on the risk of non-fatal haemorrhagic and thromboembolic stroke, we carried out a case-control study. METHODS: From the Danish National Patient Register we identified all Danish women aged 45-64 years who had a non-fatal, first-ever cerebrovascular attack during 1990-92. Two age-matched controls were randomly selected for each case from the Danish National Person Register. Important correlates of hormone use and stroke, on which information was obtained from postal questionnaires, were controlled for by multivariate analyses based on log-linear graphical models. The analyses included data on 1422 cases classified in four subtypes of stroke (160 subarachnoid haemorrhage, 95 intracerebral haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement therapy and non-fatal subarachnoid haemorrhage (odds ratio 0.52 [95% CI 0.23-1.22]), intracerebral haemorrhage (0.15 [0.02-1.09]), or thromboembolic infarction (1.16 [0.86-1.58]), respectively, compared with never use. Current use of combined oestrogen-progestagen replacement therapy had no significant influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years.

Case-Control Studies↗