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B Stoffel-Wagner

Publications and source records attributed to B Stoffel-Wagner.

At least 19 recordsLinked to original sources
PubMed2000

Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy.

PURPOSE: The hippocampus is one of the principal target areas for neurosteroidal action, and the major neuroendocrine conversion of progesterone appears to be 5alpha-reduction and 3alpha-hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3alpha,5alpha-tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR), we studied the expression of 5alpha-reductase types 1 and 2 and 3alpha-HSOR types 1 and 2 in the resected hippocampi of patients with medically intractable chronic temporal lobe epilepsy. METHODS: We studied tissue specimens from the hippocampi of 13 women, 25 men, and four children. Quantification of different mRNAs was achieved by competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: 5Alpha-reductase 1 mRNA and 3alpha-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5alpha-reductase 2 mRNA and 3alpha-HSOR 1 mRNA were not expressed. Neither 5alpha-reductase 1 mRNA nor 3alpha-HSOR 2 mRNA concentrations in hippocampal tissue showed any statistically significant differences between women and men or between children and adults. CONCLUSIONS: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 5alpha-reductase and the type 2 isozyme of 3alpha-HSOR in the human hippocampus. The finding that both 5alpha-reductase and 3alpha-HSOR are present in the hippocampus leads us to assume the synthesis of neuroactive steroids in this human brain area.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Expression of cytochrome P450scc mRNA in the hippocampus of patients with temporal lobe epilepsy.

The hippocampus is one of the target areas of neurosteroidal action. Expression of cytochrome P450scc (P450scc, CYP11A1), one of the key enzymes in steroid metabolism, results in de novo synthesis of the neurosteroid pregnenolone. We used a competitive RT-PCR assay to quantify the amount of P450scc mRNA in hippocampal tissue specimens obtained at neurosurgery from patients with temporal lobe epilepsy (TLE). P450scc mRNA is expressed approximately 200 times lower in the hippocampus than in adrenal tissue known for high P450scc expression. P450scc mRNA concentrations were significantly higher in the hippocampus of women (1.72 +/- 0.36 aU, arbitrary units; mean +/- s.e.m.) than of men (0.92 +/- 0.15 aU, p < 0.004). Our data show for the first time the sex-dependent expression of P450scc mRNA in the hippocampus of patients with TLE.

Adrenal Glands↗
PubMed1999

Analysis of the MEN1 gene in sporadic pituitary adenomas.

The MEN1 gene on chromosome 11q13 is mutated in patients afflicted with multiple endocrine neoplasia syndrome type 1 (MEN1). These patients develop endocrine tumours of the pancreas, the parathyroid, and the anterior pituitary. In order to determine the role of MEN1 in sporadic pituitary adenomas, 61 pituitary adenomas were analysed from patients without evidence of a familial tumour syndrome. Single strand conformation polymorphism (SSCP) analysis was performed for the entire coding sequence of MEN1. Fragments with aberrant migration patterns were sequenced bidirectionally. Only a single somatic mutation was detected in this series. In addition, several previously reported and three novel polymorphisms were observed. Loss of heterozygosity analysis with 12 polymorphic markers, however, identified 13 pituitary adenomas with allelic deletions on chromosome 11. Allelic losses occurred significantly more often in pituitary adenomas with hormone secretion than in non-functioning adenomas. These data suggest that MEN1 mutations are rare events in sporadic pituitary adenomas. However, the discrepancy of only 1/61 adenomas with MEN1 mutation but 13/61 (22 per cent) with allelic loss on chromosome 11 may suggest the presence of a yet unknown tumour suppressor gene, relevant to the pathogenesis of sporadic pituitary adenomas.

Adenoma↗
PubMed1999

Does octreotide treatment improve the surgical results of macro-adenomas in acromegaly? A randomized study.

It is not clear whether the pre-operative treatment of GH-secreting pituitary adenomas with Octreotide improves the surgical remission rates of acromegaly. In a prospective controlled study the results of transsphenoidal surgery in newly diagnosed GH-secreting macro-adenomas were compared in patients with (n = 11, group A) and without (n = 13, group B) preoperative Octreotide treatment. During the treatment with a daily dosage of 470 +/- 160 micrograms Octreotide for 16.5 +/- 10 weeks, the GH- and IGF-1-values of group A dropped significantly from 38.9 +/- 34.1 to 6.8 +/- 4.9 micrograms/l and from 2.7 +/- 1 to 1.7 +/- 0.7 arbitrary units respectively. The adenoma-shrinkage from 5.9 +/- 5.8 to 4.7 +/- 4.9 cm3 missed statistical significance by little. There was no statistically significant difference between the postoperative acromegaly remission rates of 55% in group A and 69% in group B. Of the adenomas that postoperatively were not in remission, 80% in group A and 75% in group B disclosed an infiltrative growth pattern not influenced by the Octreotide pretreatment. All other patients not cured presented with initial GH-values of > 50 micrograms/l. There was no statistically significant difference between the postoperative anterior pituitary function in the two patient groups. In this study Octreotide was not beneficial in improving the results of GH-secreting pituitary macro-adenoma surgery. However, larger prospective controlled studies are needed to address this issue.

Acromegaly↗
PubMed1999

Characterization of 17beta-hydroxysteroid dehydrogenase activity in brain tissue: testosterone formation in the human temporal lobe.

Sex steroids exert important effects on the central nervous system (CNS). Although the formation of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) metabolites in the CNS was discovered almost 30 years ago, conclusive studies concerning 17beta-HSD activity in the human brain are still lacking. Therefore, we investigated 17beta-HSD in vitro activity in human temporal lobe biopsies of 13 women and 13 men using radioactively labelled androstenedione, testosterone, oestrone and 17beta-oestradiol and compared it to that in human placenta, liver, testis and prostate. We could demonstrate androgenic and oestrogenic 17beta-HSD activities in all tissues under investigation. The reduction of androstenedione and oestrone in brain was NADPH dependent with a broad pH optimum between 6.5 and 9.0, whereas the oxidation of testosterone and 17beta-oestradiol was NAD dependent with a pH optimum of >/=9.0. Using optimum cofactors sex differences of brain 17beta-HSD activities were not observed. Conversion of androstenedione, testosterone, oestrone and 17beta-oestradiol was significantly higher in the subcortical white matter than in the cerebral cortex. We could demonstrate a significant formation of testosterone in the brain tissue of all patients under investigation. Substrate specificity and cofactor requirement patterns as well as pH optima and kinetic properties suggest the occurrence of 17beta-HSD type 3 and type 4 in the human temporal lobe.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Sex- and age-specific differences in human brain CYP11A1 mRNA expression.

While the presence of CYP11A1 (P450SCC, cholesterol side-chain cleavage enzyme) has been well established in the brain of rodents, limited information is available on CYP11A1 expression in human brain. In both species, little is known regarding postnatal changes or sex specific differences in cerebral CYP11A1 expression. In the present study, we used a sensitive competitive reverse transcriptase polymerase chain reaction (RT-PCR) assay to quantify the amount of CYP11A1 mRNA in a large number of human brain tissue specimens obtained at neurosurgery. CYP11A1 mRNA is expressed approximately 200 times lower in the temporal lobe, frontal lobe and hippocampus than in adrenal tissue, known for high CYP11A1 mRNA expression. During childhood CYP11A1 mRNA concentrations in the temporal lobe increase markedly and reach adult levels at puberty. CYP11A1 mRNA is significantly higher in the temporal and frontal lobe cortex of women than in that of men. Our data demonstrate for the first time an age and sex dependent expression of CYP11A1 mRNA in the human brain.

Adrenal Glands↗
PubMed1999

Characterization of aromatase cytochrome P450 activity in the human temporal lobe.

Local aromatase-mediated conversion of androgens plays an important role in androgen action on the brain. To characterize estrogen formation in the human brain, we measured the microsomal aromatase activity of temporal lobe biopsies and compared it to that of human placenta using a highly sensitive 3H2O assay with [1beta-3H]androstenedione as substrate. Brain tissue was removed neurosurgically from 23 patients with epilepsy. Data of kinetic studies were analyzed with a computer-assisted, nonlinear, curve-fitting method using the Michaelis-Menten plus a nonspecific metabolism model. In contrast to data for placental aromatase activity, that for brain always had to be corrected for nonspecific tritium release. The mean K, values were 22.2 nmol/L in brain and 49.6 nmol/L in placenta. Inhibition experiments with atamestane, an inhibitor of aromatase cytochrome P450, revealed specific, dose-responsive, and competitive inhibition of both brain and placental aromatase activities. Placental aromatase activity was completely suppressible by atamestane, whereas in brain tissue there remained a residue of nonspecific tritium release. Subsequent experiments with cerebral cortex and subcortical white matter specimens of children and adults revealed a significantly higher aromatase activity in cerebral cortex than in subcortical white matter, but no sex or age differences were found.

Adolescent↗
PubMed1999

Expression of 17beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe.

Sex steroid hormones exert important biological effects on the brain. Moreover, an extensive sex steroid metabolism occurs in the brain. In sex steroid metabolism 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play essential roles in catalyzing the final steps in androgen and estrogen biosynthesis. Recently four types of human 17beta-HSDs and a pseudogene of the type 1 isoform were identified. To date, 17beta-HSD has not been extensively studied in the human brain. Therefore, we investigated the mRNA expression of the four isozymes of 17beta-HSD as well as the pseudogene of the type 1 isoform in the human temporal lobe to determine the predominant isoforms and, moreover, to elucidate the existence of possible sex and age differences. We studied biopsy materials from the temporal lobe of 34 women, 32 men and 10 children. Quantification of different mRNAs was achieved by competitive reverse transcription-PCR. 17beta-HSD 1, 17beta-HSD 3 and 17beta-HSD 4 were expressed in the human temporal lobe of children and adults, whereas 17beta-HSD 2 and the pseudogene of 17beta-HSD 1 were not expressed. In adults, 17beta-HSD 3 and 17beta-HSD 4 mRNA concentrations were significantly higher in the subcortical white matter (17beta-HSD 3: 14 591+/-3457 arbitrary units (aU), mean+/-s.e.m.; 17beta-HSD 4: 1201+/-212 aU) than in the cortex (17beta-HSD 3: 5428+/-1057 aU, P<0. 0002; 17beta-HSD 4: 675+/-74 aU, P<0.004). 17beta-HSD 1 concentrations did not differ significantly between the white matter (3860+/-1628 aU) and the cortex (2525+/-398 aU) of adults. In conclusion, the present study demonstrates the expression of 17beta-HSD 1, 3 and 4 mRNAs in the human temporal lobe. Together with CYP19AROM and 5alpha-reductase, known to be expressed in the human brain, the expression of 17beta-HSD 1, 3 and 4 mRNAs indicates the major importance of local steroid biosynthesis in the brain.

17-Hydroxysteroid Dehydrogenases↗
PubMed1998

Expression of CYP19 (aromatase) mRNA in the human temporal lobe.

The conversion of androgens to estrogens by CYP19 (cytochrome P450AROM, aromatase) is an important step in the mechanism of androgen action in the brain. CYP19 expression has been demonstrated in various animal species, but studies in human postnatal brain tissue are lacking. Therefore, we investigated CYP19 mRNA expression in human temporal lobe tissues. We studied biopsy materials removed at neurosurgery from 34 women, 32 men and 10 children with temporal lobe epilepsy. Quantification of CYP19 mRNA was achieved by nested competitive reverse transcription-PCR. CYP19 mRNA concentrations did not differ significantly between women (2.6 +/- 0.6 arbitrary units, aU; mean +/- SEM) and men (1.6 +/- 0.3 aU) nor between cerebral cortex tissue (2.0 +/- 0.4 aU) and subcortical white matter tissue of adults (2.4 +/- 0.7 aU), but they were significantly lower in cerebral cortex specimens of children (0.9 +/- 0.6 aU) than in those of adults (p < 0.02). In conclusion, CYP19 mRNA is expressed in the temporal lobe of children and adults. CYP19 mRNA concentrations are significantly lower in specimens of children than in those of adults.

Adult↗
PubMed1998

Pretreatment follicle-stimulating hormone: a prognostic serum marker of spermatogenesis status in patients treated for germ cell cancer.

PURPOSE: We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio. MATERIALS AND METHODS: Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy. RESULTS: Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation. CONCLUSIONS: Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.

Adult↗
PubMed1998

Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication.

PURPOSE: To evaluate the changes in serum sex hormones of gonadal or adrenal origin, the gonadotropic hormones, and sex hormone-binding globulin (SHBG) in men and women with chronic temporal lobe epilepsy (TLE), who are undergoing monotherapy with carbamazepine or receiving carbamazepine in combination with other anticonvulsant drugs. METHODS: Gonadal hormones (estradiol, testosterone, free testosterone, and inhibin B), adrenal hormones [cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17alpha-hydroxyprogesterone], and gonadotropic hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) were measured in 22 women and 26 men with TLE. The study also measured prolactin; human growth hormone and its major mediator, insulin-like growth factor-I; thyroid hormones (free thyroxine and free triiodothyronine); thyroid-stimulating hormone (TSH); and SHBG. The results were compared with those obtained from 60 healthy women and 106 healthy men. RESULTS: In the female patients, TSH, DHEAS, follicular-phase LH, and luteal-phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17alpha-hydroxyprogesterone, free testosterone, inhibin B, and the testosterone/LH ratio were significantly lower than in the control group, with LH, FSH, and SHBG significantly higher. Increased FSH in 31% of the men indicates an impairment of spermatogenesis; lowered inhibin B in 12% indicates an impaired Sertoli's cell function; and the decreased testosterone/LH ratio in 50% indicates an impaired Leydig's cell function. CONCLUSIONS: The case patients had endocrine disorders, mainly concerning the gonadotropic and gonadal functions in both sexes; the adrenal function, with lowered DHEAS levels in both sexes; and lowered 17alpha-hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.

Adult↗
PubMed1998

Expression of 5alpha-reductase in the human temporal lobe of children and adults.

Androgens exert important biological effects on the brain, and 5alpha-reductase plays a crucial role in androgen metabolism. Therefore, we investigated the expression of the two isozymes of 5alpha-reductase in the human temporal lobe to determine the predominant isoform and to elucidate the existence of possible sex differences and differences between children and adults. We studied biopsy materials from the temporal lobe of 34 women, 32 men, and 12 children. Quantification of 5alpha-reductase 1 and 2 messenger ribonucleic acid (mRNA) was achieved by competitive RT-PCR. 5Alpha-reductase activity was determined in tissue homogenates using [1,2-3H]androstenedione as the substrate. Only 5alpha-reductase 1 mRNA was expressed in human temporal lobe tissue; 5alpha-reductase 2 mRNA was not expressed. 5Alpha-reductase 1 mRNA concentrations did not differ significantly in the cerebral cortex of women [25.9+/-7.9 arbitrary units (aU); mean +/-SEM] and men (20.4+/-2.8 aU) or in the cerebral cortex (23.3+/-4.4 aU) and the subcortical white matter of adults (32.6+/-5.6 aU), but they were significantly higher in the cerebral cortex of adults than in that of children (6.4+/-2.3 aU; P < 0.005). The apparent Km of 5alpha-reduction did not show significant differences between the two sexes. In conclusion, 5alpha-reductase 1 mRNA is expressed in the temporal lobe of children and adults, but 5alpha-reductase 2 mRNA is not. 5Alpha-reductase 1 mRNA concentrations did not differ significantly in the sexes, but they were significantly higher in specimens of adults than in those of children.

Adult↗
PubMed1997

An optimized protocol for mRNA quantification using nested competitive RT-PCR.

Nested competitive reverse transcription polymerase chain reaction is an effective tool for the quantification of low level expressed mRNAs. Competitive RNA standards with small deletions allow the use cRT-PCR. The sensitivity is further increased by the utilization of nested PCR protocols. To optimize quantification of low abundance mRNAs we modified established protocols for use of automated labstations and semiautomated sequencers. In placental tissue, known for a very high CYP19 (P450AROM, aromatase) expression, cRT-PCR and nested cRT-PCR yielded virtually identical results which could be confirmed by Northern blotting. CYP19 mRNA in breast tumour tissue ranged below detection levels for Northern blotting; however, using our modified assay CYP19 showed 1.5 to 15 fold higher expression levels than in normal glandular breast tissue. Our approach proved to be useful for the quantification of a gene with low level expression. The employment of labstations and semiautomated sequencers allows rapid analysis of large sample numbers.

Aromatase↗
PubMed1997

[Initial symptoms and anamnestic time in 517 patients with pituitary adenoma].

OBJECTIVE: To find out whether recent techniques of investigating hypophyseal adenoma (computed tomography, magnetic resonance imaging and hormonal measurements) have brought about earlier diagnosis. PATIENTS AND METHODS: The time of onset of first symptoms and the duration from first symptoms to diagnosis (anamnestic time) were determined retrospectively from clinical, endocrinological, ophthalmological and localizing data on 517 patients (311 women, 206 men) with hypophyseal adenoma. RESULTS: The most common initial symptom was oligo- or amenorrhoea, in 57.9% of women, and disturbed libido or potency in 38.5% of men. Next most common were visual field deficits (women: 11.6%, men: 26.7%), signs of acromegaly (women: 11.3%, men 18.2%) and headaches (women: 11.3%, men 15.5%). The median anamnestic time in women, 3.0 years, was significantly longer than the 2.3 years in men (P < 0.001). In hormonally inactive adenoma the corresponding times were 2.0 years in women and 1.0 year in men; in prolactinoma 4.2 years and 2.0 years; in growth-hormone secreting adenoma 5.0 years and 5.5; and in ACTH-secreting adenoma 5.0 years and 1.0 year. CONCLUSIONS: Although diagnostic techniques have greatly improved, the anamnestic time for hypophyseal adenoma is not shorter than in earlier studies. This findings underlines the need for clearly directed history-taking and for good training in endocrinology.

Acromegaly↗
PubMed1997

Renal functional reserve and nitric oxide in patients with compensated liver cirrhosis.

To investigate the role of nitric oxide (NO) with respect to kidney function and liver cirrhosis, we evaluated renal function, as well as cyclic guanosine monophosphate (cGMP) and NOx (nitrite/nitrate [NO3-/NO2-]) as indirect markers of NO formation in plasma and urine at rest and during amino acid (aa)-induced glomerular hyperfiltration in patients with Child A liver cirrhosis and portal hypertension (n = 12), and in healthy controls (n = 10). Baseline filtration rate (GFR) and effective renal plasma flow (ERPF) were significantly lower in patients with cirrhosis than in controls (GFR: mean 88 +/- SD 16 mL/min vs. 106 +/- 15 mL/min, P = .01, ERPF: 477 +/- 93 vs. 561 +/- 72 mL/min, P = .002). In both groups amino acid (aa) infusion increased GFR, ERPF, as well as cGMP and urinary NOx. Changes in GFR were similar in cirrhotic patients and controls (28.3% +/- 14% in cirrhotics and 26% +/- 11% in controls), but the degree of aa-induced changes in ERPF was more marked in patients with liver cirrhosis (31.8% +/- 17% vs. 18.6% +/- 12%, P = .02). Plasma levels of NOx and cGMP were similar in either group at baseline and during aa infusion, whereas NOx and cGMP excretion in cirrhotics was constantly 14% to 24% lower than in the control group. We conclude that patients with compensated liver cirrhosis and portal hypertension already have an impaired kidney function. In addition our data suggest a cirrhosis-related dissociation between ERPF and GFR during aa stimulation. Further studies are warranted to find out whether a local imbalance between vasoconstrictors and vasodilators, e.g., decreased local NO formation, plays a key role for this phenomenon.

Adult↗
PubMed1997

A comparison of different methods for diagnosing acromegaly.

OBJECTIVE: The present study was designed to assess the diagnostic value of different single measurements in comparison to the classic time-consuming method, the oral glucose tolerance test (OGTT), in acromegaly. DESIGN, PATIENTS AND MEASUREMENTS: IGF-I, free IGF-I, 24-hour-urinary GH (uGH), serum IGFBP-3 and 24-hour-urinary IGFBP-3 (uIGFBP-3) were measured in 12 patients with untreated active acromegaly, in 29 patients who had been treated but were not cured, in 13 patients with cured acromegaly and in 14 healthy control subjects, and compared with the results of the OGTT. RESULTS: In all patients with active acromegaly, whether they had been treated or not, nadir GH in OGTT was > 3 mU/l, whereas nadir GH was < 1.8 mU/l in the cured patients and the control subjects. In patients with untreated active acromegaly IGF-I, free IGF-I, uGH and IGFBP-3, but not uIGFBP-3, were significantly higher than in healthy individuals (P < 0.0001). Only IGF-I values did not overlap with the control group. In those patients with acromegaly who had been treated but not cured these parameters overlapped with the control group. In patients with acromegaly there was a significant correlation between nadir GH levels in OGTT and IGF-I (r = 0.71), free IGF-I (r = 0.76), IGFBP-3 (t = 0.73) and uGH (r = 0.81) (P < 0.0001), but no correlation with uIGFBP-3. CONCLUSIONS: Only be means of the OGTT could patients with active acromegaly be completely distinguished from the control subjects and from cured patients. IGF-I, free IGF-I, IGFBP-3 and uGH were useful in the diagnosis of acromegaly, but of limited value in the follow-up of acromegalic patients after treatment. The determination of free IGF-I, which has yet not been investigated in acromegaly, offered no advantage over that of total IGF-I and IGFBP-3; uIGFBP-3 was not useful in the diagnosis of acromegaly.

Acromegaly↗
PubMed1997

Gonadal function of patients treated with cisplatin based chemotherapy for germ cell cancer.

PURPOSE: The cure rate of patients with germ cell cancer of the testis has considerably improved since the introduction of cisplatin based chemotherapy. Because these patients are in their reproductive years and because some of them will be infertile after treatment, the effects of cytotoxic treatment on gonadal function are investigated by hormonal evaluations. MATERIALS AND METHODS: In a transversal trial, luteinizing hormone, follicle-stimulating hormone and testosterone were determined radioimmunologically in serum samples of 232 patients with germ cell tumors after unilateral orchiectomy (patient age 18 to 64 years) up to 153 months after chemotherapy. Additionally, 51 of these patients were investigated in a longitudinal trial before and up to 5 years after chemotherapy. All patients received at least 2 courses of different cisplatin based chemotherapy regimens: cisplatin/vinblastine/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide/etoposide. Additionally, 11 patients with germ cell tumors (age 22 to 38 years, stage I) were investigated within the first year after orchiectomy and retroperitoneal lymphadenectomy but without chemotherapy. RESULTS: In the transversal trial, 24 of 73 patients investigated during the first year after chemotherapy showed elevated luteinizing hormone concentrations, 5 had subnormal serum testosterone and 65 had elevated serum follicle-stimulating hormone, reflecting spermatogenesis deficits. In 28 patients studied longer than 8 years after chemotherapy (median followup 8.5 years, range 8.0 to 12.6), luteinizing hormone increased after chemotherapy and 60 months after treatment, and follicle-stimulating hormone was elevated in 1 patient, follicle-stimulating hormone was increased in 18 and testosterone was subnormal in 1. Patients without chemotherapy treatment showed gonadotropin and testosterone within normal range and 3 patients had elevated serum follicle-stimulating hormone. In the longitudinal study, mean serum luteinizing hormone plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating hormone (7.79 +/- 0.13 IU/l.) and testosterone (18.6 +/- 0.17 nmol./l.) were within the normal range before chemotherapy; serum follicle-stimulating hormone was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p < 0.001). Mean luteinizing hormone and testosterone levels were within the normal range, but 60 months after therapy the testosterone-to-luteinizing hormone ratio was still lower than before treatment (p < 0.05). CONCLUSIONS: In patients with germ cell tumors, a compensated insufficiency of the function of the Leydig cells was still observed up to 60 months after chemotherapy. Of these patients 68% showed elevated follicle-stimulating hormone levels, which reflected a functional insufficiency of the Sertoli cells with impaired spermatogenesis. This study shows that impairment of germinative functions is more severe and protracted than the impairment of the endocrine functions.

Adolescent↗