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Biomedical subjects

A J Pakarinen

Publications and source records attributed to A J Pakarinen.

34 records · Page 2Linked to original sources

Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy.

BACKGROUND: Reproductive endocrine disorders are more common among women with epilepsy than among normal women. These disorders have been attributed to epilepsy itself, but could be related to antiepileptic-drug therapy. METHODS: We studied 238 women with epilepsy who were seen regularly at the Outpatient Department of the University Hospital, Oulu, Finland. Their mean age was 33 years (range, 18 to 45), and the mean duration of therapy was 9 years (range, 0 to 31). Twenty-nine (12 percent) were treated with valproate, 120 (50 percent) with carbamazepine, 12 (5 percent) with valproate and carbamazepine, and 62 (26 percent) with other medications; 15 (6 percent) were untreated. Vaginal ultrasonography was performed to determine ovarian size, and serum sex-hormone concentrations were measured in 41 women with epilepsy and menstrual disturbances, 57 women with epilepsy and regular menstrual cycles, and 51 normal women. RESULTS: Menstrual disturbances were present in 13 of the women receiving valproate alone (45 percent), 3 of the women receiving valproate in combination with carbamazepine (25 percent), 23 of the women receiving carbamazepine (19 percent), and 8 of those receiving other medications (13 percent). Forty-three percent of the women receiving valproate had polycystic ovaries, and 17 percent had elevated serum testosterone concentrations without polycystic ovaries; 50 percent of the women receiving valproate and carbamazepine had polycystic ovaries, and 38 percent had elevated serum testosterone concentrations without polycystic ovaries. Eighty percent of the women treated with valproate before the age of 20 years had polycystic ovaries of hyperandrogenism. CONCLUSIONS: Menstrual disturbances, polycystic ovaries, and hyperandrogenism are often encountered in women taking valproate for epilepsy.

Adolescent↗

Serum lipid levels during carbamazepine medication. A prospective study.

OBJECTIVE: The aim of the study was to evaluate serum lipid levels during carbamazepine medication. DESIGN: A 5-year prospective follow-up study. SETTING: Outpatient department, University Central Hospital of Oulu (Finland). PATIENTS: Thirty-six consecutive untreated patients with recently diagnosed idiopathic epilepsy. All patients completed the 1-year follow-up, and 19 patients completed the 5-year follow-up. INTERVENTIONS: The patients were treated with carbamazepine for their newly diagnosed seizure disorder. MAIN OUTCOME MEASURES: Serum lipid levels were followed up during the medication use. RESULTS: Serum total cholesterol and high-density lipoprotein cholesterol concentrations increased after 2 months of treatment with carbamazepine and remained high after 1 and 5 years. Furthermore, concentrations of serum low-density lipoprotein cholesterol and triglycerides increased transiently during the first year of medication. The increase in serum total cholesterol levels correlated with an increase in serum gamma-glutamyltransferase concentrations. CONCLUSIONS: Serum lipid levels change during carbamazepine medication; the increase in serum concentrations of total cholesterol and high-density lipoprotein cholesterol seems permanent, but the increase in serum low-density lipoprotein cholesterol and triglyceride levels is transient. The change in lipid metabolism may be associated with induction of the liver enzymes during carbamazepine medication. The increase in serum cholesterol and high-density lipoprotein cholesterol levels may have clinical relevance with regard to the incidence of atherosclerosis and coronary heart disease in patients with epilepsy receiving carbamazepine medication.

Adolescent↗

Carbamazepine, serum thyroid hormones and myocardial function in epileptic patients.

Serum thyroid hormone and thyrotropin levels were assayed and the myocardial function was evaluated by measuring systolic time intervals both in 30 patients with epilepsy on long-term carbamazepine monotherapy and in 19 healthy volunteers. Serum thyroxine, free thyroxine and triiodothyronine levels were significantly lower (p < 0.001) in the patient group than in the control group and systolic time intervals were similar in both groups.

Adult↗

A prospective study of serum sex hormones during carbamazepine therapy.

This paper reports the results of a 12-month prospective follow-up study on the effects of carbamazepine (CBZ) medication on serum sex and pituitary hormone concentrations in 21 male patients with recently diagnosed epilepsy. The results of the present study indicate that a change occurs in the androgen balance during CBZ medication in male patients with epilepsy: a rise in serum sex hormone binding globulin levels results in decreased free androgen index values, and dehydroepiandrosterone sulfate serum levels decrease. Serum testosterone and free testosterone levels remain unchanged, but estradiol levels decrease. Serum basal prolactin (PRL) levels remain unchanged, but the PRL responses to thyrotropin-releasing hormone and metoclopramide increase slightly during the first year of CBZ medication. Basal and stimulated serum gonadotropin levels remain unchanged. The clinical consequences of these hormonal changes during CBZ medication call for further studies.

Adolescent↗

Serum hormones in male epileptic patients receiving anticonvulsant medication.

Circulating sex and thyroid hormones, as well as the pituitary function, were assessed in 63 male patients with epilepsy receiving either a single medication of carbamazepine, phenytoin, or valproate or a combination of carbamazepine plus phenytoin or carbamazepine plus valproate. All therapeutic regimens, including carbamazepine and/or phenytoin were associated with low levels of circulating thyroxine (T4), free thyroxine (FT4), and dehydroepiandrosterone sulfate, and with low values for the free androgen index, and phenytoin and carbamazepine plus phenytoin were associated with high serum concentrations of sex hormone-binding globulin. These hormone parameters were unaffected by valproate monotherapy. It seems probable that accelerated hormone metabolism is responsible for the hormonal changes found in patients treated with carbamazepine and/or phenytoin. However, every drug regimen studied also had depressant and/or stimulatory effects on the function of the hypothalamic-pituitary axis. The diverse endocrine effects of different antiepileptic drug regimens should be considered when starting antiepileptic drug therapy.

Adolescent↗

Thyroid function in epileptic patients treated with carbamazepine.

The effects of carbamazepine monotherapy on thyroid function were evaluated in patients with epilepsy. A prospective follow-up of 40 patients with recently diagnosed epilepsy was carried out to evaluate the short-term effects. Thirty-three patients receiving long-term carbamazepine therapy (average duration, 4.2 years) and 34 healthy control subjects were studied. Levels of serum thyroxine, free thyroxine, and thyroxine binding globulin were decreased after both 2 and 12 months of therapy with carbamazepine. Low serum thyroxine and free thyroxine concentrations were also found after long-term monotherapy with carbamazepine. Baseline thyrotropin did not change during carbamazepine therapy, but thyrotropin responses to thyrotropin-releasing hormone rose slightly. No correlation was found between serum carbamazepine and hormone concentrations. The results not only support previous suggestions that carbamazepine induces the hepatic clearance of thyroid hormones but also suggest that carbamazepine may have an inhibitory effect at the hypothalamic level.

Adolescent↗

Adrenocortical function of female endurance runners and joggers.

The aim of the present study was to investigate the long-term effects of endurance exercise on the function of the adrenal cortex of 18 female runners, 12 control subjects, and 13 joggers and their 11 control subjects by measuring the serum concentrations of cortisol and dehydroepiandrosterone sulfate and the responses of cortisol to intravenous ACTH injection. All of the participants were studied over one menstrual cycle, during a light training period in the autumn and a hard training period in the spring. There were no significant between-group differences in the concentrations of cortisol in the autumn or the spring. However, the mean spring vs autumn concentrations of cortisol were significantly increased in runners during the follicular and luteal phases of the menstrual cycle. The concentrations of cortisol in the ACTH response test were also increased at 30 and 60 min in runners and all the time in joggers in spring, in relation to the respective values in the autumn. The absolute and relative rises of cortisol in response to ACTH did not differ between the groups, but the relative spring vs autumn increase of cortisol was significantly higher at 60 min in the runners and lower at 30 min in the control subjects of the joggers. There were no differences in the serum concentrations of dehydroepiandrosterone sulfate between the groups, or between spring and autumn values in any group. In conclusion, chronic endurance exercise per se did not appear to alter the function of the adrenal cortex, while an undefined spring-associated factor, possibly the high luminosity, appeared to induce an increase in cortisol secretion in female runners.

Adrenal Cortex↗

Effects of whole body massage on serum protein, electrolyte and hormone concentrations, enzyme activities, and hematological parameters.

The effects of a 1-h whole body massage on blood parameters were studied in nine healthy male volunteers. The venous blood samples were drawn just before treatment, immediately after, and after 2, 24, and 48 h. The parameters measured were blood leukocyte and erythrocyte counts, hemoglobin concentration, hematocrit, red cell indices, the activities of serum creatine kinase, lactate dehydrogenase and their isoenzymes, and the concentrations of serum sodium, potassium, total protein, haptoglobin, growth hormone, prolactin, cortisol, and plasma corticotropin. Decreases in serum haptoglobin concentrations suggested slight hemolysis. The rises in the activities of creatine kinase, lactate dehydrogenase, and its isoenzymes LDH4 and LDH5 and in the concentrations of serum potassium are indicative of increased permeability of the muscle cells. No statistically significant changes were seen for the other parameters. There were large individual variabilities in the hormone concentrations after massage, but some trends could be seen.

Blood Proteins↗

Pharmacokinetics of digoxin in patients with acute myocardial infarction.

The effects of acute myocardial infarction on the pharmacokinetics of digoxin were studied. Digoxin, 0.75 mg, was given orally to 12 patients with left-sided cardiac failure due to acute myocardial infarction and to 9 healthy control subjects. Serum concentration of digoxin in the first 4 hours and the area under the serum concentration-time curve in the first 12 hours after administration of the drug were lower in patients with infarction than in control subjects (P less than 0.01). The 24 hour area under the concentration curve, the amount excreted in urine and the renal clearance did not differ between the groups. The 24 hour area under the concentration curve correlated with the predigoxin pulmonary capillary wedge pressure and with heart rate (P less than 0.01). The decrease of renal clearance of digoxin was related to the serum activity of MB isoenzyme of creatine kinase (P less than 0.001). Morphine reduced and delayed the peak serum concentrations of digoxin (P less than 0.001). Thus, the absorption of oral digoxin was slower and the peak concentrations remained lower in patients with acute myocardial infarction than in healthy control subjects. However, the total amount of digoxin absorbed was unchanged.

Administration, Oral↗

Plasma renin, angiotensin II, and plasma and urinary aldosterone in running exercise.

Plasma renin activity (PRA), renin concentration (PRC), angiotensin II and urinary aldosterone of four male athletes were investigated before and after a running exercise of 3 X 300 m. After the exercise, there were marked increases in all these parameters. The maximal increases (of the means and the ranges), found in the samples taken 30 min after the exercise, were: 108% (27-230%, P less than 0.05) in PRA, 490% (240-800%, P less than 0.01) in PRC, 830% (400-1,970%, P less than 0.025) in plasma angiotensin II and 1,600% (160-3,920%, P less than 0.02) in plasma aldosterone. The increase in the urinary excretion of aldosterone was 120% (42-180%, P less than 0.025). This study demonstrates that intense physical exercise may cause marked changes in all the three main components of the renin-angiotensin-aldosterone system. The significance of these changes for the physiological function of the human organism in physical stress needs further investigation.

Adult↗

Plasma renin activity, angiotensin II, and aldosterone during intense heat stress.

Plasma renin activity (PRA), angiotensin II, and aldosterone levels, arterial blood pressure, and heart rate of six male students were investigated during and after heat stress in a sauna bath. Increased PRA, angiotensin II, and aldosterone levels were found both during and after sauna. The greatest mean increases in PRA (94.9 +/- 10.4% SE, P less than 0.005) and angiotensin II (196 +/- 54.7% SE, P less than 0.02) were observed at the end of the heat stress (at 20 min), and that in plasma aldosterone (505 +/- 209% SE, P less than 0.02) 30 min after the sauna. The heart rate roughly doubled during the heat stress and there was a transient increase followed by a decrease in systolic blood pressure and a decrease in diastolic blood pressure. This study demonstrates that intense heat stress can cause remarkable changes in the three main components of the renin-angiotensin-aldosterone system.

Adult↗

Effects of carbamazepine therapy on serum sex hormone levels in male patients with epilepsy.

The effects of carbamazepine (CBZ) therapy and epilepsy on sex hormone plasma levels in male patients with epilepsy were evaluated by measuring the levels of testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and dehydroepiandrosterone sulfate (DHEAS) and by calculating the free androgen index (FAI) in 23 male patients with epilepsy receiving CBZ medication, in 18 untreated male patients with epilepsy, and in 19 healthy age-matched control subjects. No significant differences in the mean T or FT levels were found between the three groups, but the CBZ-treated patients had significantly higher SHBG levels and their FAI values and DHEAS concentrations were lower. The LH, FSH, PRL, or E2 levels in CBZ-treated and untreated male patients with epilepsy did not differ from the controls. CBZ monotherapy does not significantly change the serum balance of sex hormones; however, CBZ clearly affects the serum levels of SHBG and DHEAS.

Adolescent↗

Effects of carbamazepine on pituitary responsiveness to luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and metoclopramide in epileptic patients.

Pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and metoclopramide (MC) was studied in 40 epileptic patients (24 men and 16 women) receiving carbamazepine (CBZ) treatment and in 29 (20 men and 9 women) untreated epileptic patients. Mean basal concentration of serum LH was significantly lower in the CBZ-treated female patients than in untreated female patients. The response of LH to LH-RH was also blunted in CBZ-treated female patients. No differences were found in basal or stimulated LH levels between the two groups of male patients. Nevertheless, the mean basal concentration of serum prolactin (PRL) was lower and the response of PRL to TRH was higher in male patients treated with CBZ. No differences were found in serum levels of follicle-stimulating hormone (FSH) or in responses of FSH to LH-RH between the CBZ-treated and untreated patients. These results indicate that CBZ has effects on pituitary responsiveness.

Carbamazepine↗

Effects of carbamazepine on the hypothalamic-pituitary-gonadal axis in male patients with epilepsy: a prospective study.

The effects of carbamazepine (CBZ) monotherapy on serum sex hormone levels and on pituitary responsiveness to various stimuli were evaluated in a prospective study with 21 male patients with epilepsy. The serum levels of testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and dehydroepiandrosterone sulfate (DHEAS) were assayed, and the free androgen index (FAI) values were calculated for each patient before and after 2-month CBZ treatment. The pituitary PRL, LH, and FSH responses to luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and metoclopramide (MC) were also measured before and after CBZ treatment. The baseline serum hormone and SHBG levels were measured and the FAI values calculated in 16 healthy male control subjects of similar age. The mean E2 level was higher in patients before CBZ treatment than in control subjects, and untreated patients had greater variances for FAI values, PRL levels, and LH levels than control subjects. No other significant differences were found between untreated patients and control subjects. The FAI values and DHEAS levels of patients decreased during 2-month treatment with CBZ. The PRL response to MC was higher after CBZ treatment than before. The baseline levels of other hormones and SHBG, as well as the LH and FSH responses to LH-RH, remained unaltered. The results indicate that during the first 2 months of CBZ treatment the androgen balance in male epileptic patients changes: Serum DHEAS levels and FAI values decrease, although FT levels remain unchanged. The clinical relevance of these hormonal changes is obscure.

Adolescent↗

Thyroid function with antiepileptic drugs.

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Liver enzyme induction and serum lipid levels after replacement of carbamazepine with oxcarbazepine.

We evaluated liver P450 enzyme system induction and serum lipid levels in a prospective follow-up study in 12 male patients with epilepsy after replacing carbamazepine (CBZ) medication with oxcarbazepine (OCBZ). Antipyrine(t1/2) increased and antipyrine(CL) decreased 2 months after the medication was changed, reflecting normalization of liver P450 enzyme system function. Furthermore, serum total cholesterol levels decreased, but serum concentrations of high-density lipoprotein (HDL)-cholesterol and triglycerides (TG) were unchanged. OCBZ may be the preferable antiepileptic drug (AED) with regard to the effects of the medication on lipid metabolism.

Adult↗