[Surgical possibilities permitted by a "3d approach" to cervical carcinoma].
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Biomedical subjects
Publications and source records attributed to M Luisi.
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Aging is related to critical changes of the hypothalamo-pituitary-adrenal function. A decline in serum DHEA levels has been demonstrated in healthy elderly subjects, while ACTH and cortisol concentrations remain at normal values. The purpose of the present study was to investigate the effect of aging on pituitary-adrenal responsiveness to hCRF in subjects of both sexes. A group of 12 physically and mentally healthy elderly subjects and a group of 12 young controls of both sexes have been selected. Blood samples were collected before and after i.v. bolus injection of hCRF; ACTH, cortisol and DHEA levels were then determined by RIA. Basal ACTH and cortisol levels did not result statistically different between controls and elderly subjects, while DHEA showed a clear and significant age-related decrease (p < 0.01). Following the hCRF injection, the responses of ACTH, cortisol and DHEA in aged subjects were higher than in young controls; ACTH (p < 0.03) and cortisol (p < 0.01) were higher in aged women than in men. The present study demonstrated that aging is associated with an increased responsiveness of ACTH, cortisol and DHEA to exogenous hCRF supply. A hyperactivation of the pituitary-adrenal secretory activity may explain the age-related of the same axis. Gender probably has a significant influence on basal and stimulated hormonal secretion. In conclusion, hCRF test may become a useful clinical tool in establishing a neuroendocrine correlation with central disturbances associated to aging.
A double-blind, randomized, group comparative study was performed in hypogonadal male patients in order to compare the effects on sexual activity and mental state of testosterone undecanoate (TU) and mesterolone (M). The TU-treated group contained 12 patients, and the M-treated group contained 14 patients. The variables of sexual activity and of mental state were scored an evaluated statistically by means of the nonparametric randomization test for 2 independent groups. TU induced a marked improvement of the sexual activity and of the mental state. After 4 weeks of treatment the effects were significantly better than in the M-treated group: libido (p less than 0.001), erections (p less than 0.01), ejaculations (p less than 0.05) and mental state (p less than 0.001).
Although the role of biogenic amines in the regulation of gonadotropin release has been studied extensively, the precise role of dopamine (DA) in stimulating LHRH and/or LH release is still controversial. In the present study 6 eugonadal women, aged 20-30, were given an LHRH infusion on day 6 of the menstrual cycle and the pattern and magnitude of LH and FSH responses were estimated. On day 6 of the next cycle, the experiment was repeated and DA was also infused beginning 60 min after the start of the LHRH infusion. Following LHRH infusion plasma LH showed a marked and significant rise with a mean peak increment at 4 h, and with a cumulative response (CR) of 9136 +/- 955 mIU/ml/6h. The pattern of FSH response tended to parallel that of LH; however, mean peak increment at 4 h and a CR of 2640 +/- 169 mIU/ml/6h were markedly lower. Plasma prolactin levels remained unchanged. Addition of DA to LHRH at 60 min evoked a significantly greater mean peak LH increment at 4 h and a CR of 15514 +/- 1836 mIU/ml/6h (p less than 0.001). There were no significant changes in either mean FSH peak at 4 h or in the CR (3257 +/- 309 mIU/ml/6h). As expected, a highly significant (p less than 0.001) decrease in circulating PRL from 12.1 +/- 3.1 to 3.0 +/- 1.5 ng/ml was seen during DA infusion. In conclusion, DA given by iv infusion enhancement LH response to LHRH in eugonadal women under the conditions of the present investigation, supporting a role for a dopaminergic component in the control of LH release in women.
OBJECTIVE: Animal data suggest that neuroactive steroids, such as 3alpha,5alpha-tetrahydroprogesterone (3a,5a-THP), dehydroepiandrosterone (DHEA), and its sulfated metabolite (DHEA-S), are involved in the modulation of eating behavior, aggressiveness, mood, and anxiety. Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by abnormal eating patterns, depressive and anxious symptoms, enhanced aggressiveness, and endocrine alterations. Previous studies reported decreased blood levels of DHEA and DHEA-S in small samples of anorexic patients, whereas no study has been performed to evaluate the secretion of these neuroactive steroids in BN as well as the production of 3alpha,5alpha-THP in both AN and BN. Therefore, we measured plasma levels of DHEA, DHEA-S, 3alpha,5alpha-THP and other hormones in patients with AN or BN and explored possible relationships between neuroactive steroids and psychopathology. METHOD: Ninety-two women participated in the study. There were 30 drug-free AN patients, 32 drug-free BN patients, and 30 age-matched, healthy control subjects. Blood samples were collected in the morning for determination of hormone levels. Eating-related psychopathology, depressive symptoms, and aggressiveness were rated by using specific psychopathological scales. RESULTS: Compared with healthy women, both AN and BN patients exhibited increased plasma levels of 3alpha,5alpha-THP, DHEA, DHEA-S, and cortisol but reduced concentrations of 17beta-estradiol. Plasma testosterone levels were decreased in anorexic women but not in bulimic women. Plasma levels of neuroactive steroids were not correlated with any clinical or demographic variable. CONCLUSIONS: These findings demonstrate increased morning plasma levels of peripheral neuroactive steroids in anorexic and bulimic patients. The relevance of such hormonal alterations to the pathophysiology of eating disorders remains to be elucidated.
Reversible temporary medical oophorectomy using long-acting agonist analogs of LH-RH was tried in three infertile patients suffering from large endometriomas of the ovary. These patients had stage IV disease according to the revised 1985 classification of the American Fertility Society. D-Ala6-des-Gly10-LH-RH propylamide (D-Ala6-LH-RH PA), in a dose of 125 micrograms, was administered intramuscularly every 48 hours to one patient, and daily to the other two patients, for 22, 17, and 14 weeks, respectively. Two patients subsequently received 100 micrograms of D-Trp6-LH-RH for 4 weeks in order to compare its efficacy with D-Ala6-LH-RH PA. Clinical controls, pelvic ultrasonography, and routine laboratory tests and hormone assays were done periodically. Ultrasonography images showed a reduction in the size of endometriomas after the second or third week of treatment. This reduction was maintained throughout and continued after the period of treatment. Suppression of the pituitary and estrogen responses was obtained rapidly, but some transient increments were occasionally found. Progesterone levels always decreased and remained in the range of the early follicular phase. Most intervals of uterine bleeding were prolonged. An evident improvement of abdominal pain, dysmenorrhea, and dyspareunia was found. Administration of D-Trp6-LH-RH was more effective than D-Ala6-LH-RH PA in most of the parameters tested. After discontinuation of treatment, all three patients had a prolonged follicular phase with a normal luteal phase during the first cycle. One woman became pregnant in the fourth cycle after discontinuation of D-Ala6-LH-RH PA and delivered a normal baby.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ten prepubertal boys, aged 6-12 years, presenting with unilateral or bilateral cryptorchidism were treated with a single i.m. injection of 100 micrograms of synthetic LHRH. In addition to the clinical effect, pituitary responsiveness was studied. Immunoreactive FSH and LH in serum were measured by radioimmunoassay. One week after the treatment a complete descent of testes occurred in the four oldest patients. In another four patients, a clear-cut improvement in their condition was seen, and, in two patients, no effect was observed. In nine patients, a significant (p less than 0.001) rise in serum FSH and LH levels was observed. In one patient, serum gonadotropin levels remained unchanged. There was no correlation between the clinical effect and pituitary responsiveness. It was concluded that i.m. administration of LHRH offers advantages over the paranasal route since the dose required for a good effect appears to be considerably lower.
The dynamics of urinary and plasma steroids (CPB and RIA) were simultaneously studied in a 36-yr-man with Cushing's syndrome due to adrenal carcinoma. The markedly increased basal excretion of 5-pregnenetriol, PG, PGT, DHA, THS and corticosteroids with nonsignificant changes during the endocrine tests decreased to normal levels after tumour removal. The basal low level of plasma testosterone, with nonsignificant changes during the endocrine tests, rose progressively after surgery. The steroid content of adrenal carcinoma tissue determined by CPB and RIA after LH-20-Sephadex CC separation revealed important proportion of unconjugated 17-OH-P.
A double-blind cross-over study with Org OD 14 and placebo was performed in 82 menopausal patients presenting with hot flushes and associated symptoms. Patients were randomly allocated to Org OD 14 or placebo as first treatment, and switched to placebo or Org OD 14 as second treatment. Each treatment period lasted for 16 weeks; no wash-out period was introduced. Tablets containing 2.5 mg of Org OD 14 or matched placebo tablets were supplied. Data on the following variables were obtained and analysed by the non-parametric randomization test for paired observations: hot flushes, sweating, dizziness, palpitations, fatiguability, headache, sleeplessness, irritability, breathlessness, backache and loss of libido and, in 16 patients, on circulating levels of FSH, LH, PRL, T3, T4, cortisol (F), SHBG, TBG and CBG. Twenty patients (13 placebo, 7 Org OD 14) withdrew, because their symptoms did not improve and one patient withdrew for reasons unrelated to treatment, so that 61 patients completed the study. The data demonstrated a good clinical effect and statistically significant differences in favour of Org OD 14 for hot flushes and a number of associated symptoms. Many patients reported on a general feeling of well being and a mood-elevating effect following Org OD 14. Org OD 14 significantly suppressed FSH and LH levels, while those of PRL remained unchanged. Although there was slight suppression of TBG and T4 which attained statistical significance, there was no influence on the most important parameter, T3. SHBG levels were slightly suppressed, whereas F and CBG levels were unaffected.
Twenty healthy male volunteers were randomly allocated to the treatment with either 15 mg/day of epimestrol or placebo for 10 days. The plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), oestradiol (E2) and prolactin (PRL) were measured before, during and 4 days after the medication by radioimmunoassays. Data were statistically evaluated by means of an analysis of covariance. Circulating LH and FSH, and also T and E2 significantly increased in the epimestrol treated subjects. In the placebo treated subjects no significant changes in the plasma hormone levels were observed. There were no significant changes in the plasma levels of PRL in either group.
Org OD 14 has recently been shown to be an interesting new steroid for the treatment of menopausal women. In view of the importance of treatment of perimenopausal women, in whom ovulation might occur, the aim of the present study was to assess whether or not Org OD 14, administered orally in a daily dose of 2.5 mg for 21 days, inhibits ovulation. Sixteen healthy female volunteers, aged 20-34 years and with established ovulatory cycles, were studied during a control cycle and a treatment cycle. Daily measurements of the plasma levels of FSH, LH, E2, P and PRL were made. Endometrial specimens were obtained from nine of the volunteers between 23rd and 25th day of both cycles. The criteria for an ovulatory cycle were: (1) mid-cycle FSH, LH and E2 peaks; (2) criteria (1) followed by a rise in the P levels of greater than 10 ng/ml; (3) a luteal phase of at least 12 days; (4) biphasic behaviour of E2; and, (5) secretory endometrium on days 23-25 of the cycle. All control cycles were ovulatory. During the treatment the mid-cycle FSH, LH and E2 peaks disappeared, and P levels remained very low. PRL levels showed an occasional moderate rise in some of the volunteers. Endometrial specimens showed a secretory pattern during the control cycle, and different degrees of proliferation during the treatment cycle in all nine volunteers. It was concluded that Org OD 14 inhibited ovulation in all 16 volunteers.
The plasma levels of CBG, TBG, SHBG and progesterone, and salivary progesterone levels were measured in eight young ovulatory volunteers. After the control cycle four subjects received 50 mg/day of Clomiphene from days 5 to 9 of the first treatment cycle, and 10 mg/day of Epimestrol from days 5 to 15 of the second treatment cycle. The other four subjects received the treatments in reverse order. Between the two treatments there was one cycle without medication as a "wash-out" period. Plasma and saliva samples were obtained on days +6, +8 and +10 (day of LH peak was denoted by 0), always between 08.00 and 09.00 h. Statistical evaluation was done by means of an analysis of variance (ANOVA), and correlation coefficients were also calculated. Evaluation of data on effects of Clomiphene and Epimestrol on the plasma levels of CBG and salivary progesterone showed that Clomiphene induced a highly significant rise (p less than 0.001) in the CBG levels and decrease (p less than 0.001) in salivary progesterone levels, while no changes were seen following administration of Epimestrol. Both Clomiphene and Epimestrol treatments led towards higher plasma progesterone levels, those following Clomiphene administration being higher. Neither treatment induced significant changes in TBG or SHBG levels. It is concluded that Clomiphene induces significant elevations of CBG and decrease in salivary progesterone, which is thought to reflect the free progesterone fraction and may have significance in relation to a discrepancy between the ovulation and pregnancy rates following Clomiphene therapy.
To study the effect of 2-hydroxyestrone (2-OHE1) on circulating prolactin (PRL) in a hyperprolactinaemic state, seven anovulatory women with hyperprolactinaemia were given a 2-OHE1 infusion at a rate of 80 microgram/h for 3 h following a control infusion. Plasma samples for PRL determination were obtained at 30-minute intervals for 6h. No changes in PRL levels were observed during the 2-OHE1 infusion as compared with the control period. It was concluded under conditions of the present experiment that 2-OHE1 does not suppress circulating PRL in hyperprolactinaemic anovulatory women.
Plasma levels of oestradiol were measured in blood samples obtained from 6 normal men every 12 minutes for two 4-hour periods: between 08.00 and 12.00h and between 18.00 and 22.00h. Circulating oestradiol was measured by radioimmunoassay after chromatographic separation on microcolumns of Sephadex LH-20. Mean values of oestradiol concentrations and coefficients of variation for two 4-hour periods were calculated for each subject and for the whole group. Data were statistically evaluated by means of the Wilcoxon signed-rank test. Rapid fluctuations in plasma oestradiol levels were observed in all subjects. The pattern of the fluctuations was found to be irregular and different in each subject. The mean concentration and coefficient of variation were significantly (p less than 0.05) higher in the morning, suggesting the possibility of a circadian rhythm in the secretion of oestradiol in men.