Patrizia Costelli

Sex Hormones and Pituitary Function in Male Epileptic Patients with Altered or Normal Sexuality

Summary Male epileptic patients frequently complain of sexual dysfunction, particularly impotence and loss of libido. Epilepsy itself, antiepileptic drugs (AEDs), and psychosocial factors are believed to contribute to impaired sexuality. We studied luteinizing hormone (LH) ulsatile secretion, gonadotropin, and prolactin (PRL) esponses to LH‐releasing hormone (LHRH) and thyrotropin‐releasing hormone (TRH) in 37 adult male epileptic patients receiving AED monotherapy who were seizure‐free and had normal EEGs. Sexuality was assessed by psychological interview. Impotence was diagnosed in 8 patients (in 2 combined with loss of sexual desire). The occurrence of hyposexuality (‐20%) was independent of epilepsy syndrome or AED. No change in total testosterone (T) level was observed. Free T (ft)and dihydrotestosterone (DHT) levels were lower and sex hormone binding globulin (SHBG) levels were higher in epileptic subjects than in healthy controls, but a statistically significant difference was not observed between hypo‐ and normosexual patients. In impotent epileptic patients, estradiol (E2) levels were significantly increased as compared with those of patients with preserved sexuality and of healthy controls. The unbalanced relation between androgen and E2 levels was emphasized by decreased fT/E2, fT/E2, and DHT/E2 ratios obtained in hyposexual epileptic patients. In this group, LHRH induced blunted LH peaks. No changes were noted in LH pulsatility features. These findings of higher E2 levels and of decreased LH response to LHRH administration in some epileptic patients with impaired sexuality, may suggest they have subclinical hypogonadotropic hypogonadism.

Urinary melatonin excretion throughout the ovarian cycle in menstrually related migraine

Nocturnal urinary melatonin excretion was significantly decreased throughout an ovarian cycle in 12 migraine without aura patients compared to 8 healthy controls. Normal increases in urinary melatonin excretion during the luteal phase was less pronounced in the migraine patients. Melatonin excretion was further decreased during headache. The data indicate impaired pineal function in migraine.

Sex hormones, gonadotropins and prolactin in male epileptic subjects in remission: Role of the epileptic syndrome and of antiepileptic drugs

Sex steroid peripheral pattern, pulsatile luteinizing hormone (LH) secretion, gonadotropin and prolactin responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) were studied in 35 male epileptics treated with phenobarbital (PB), carbamazepine (CBZ), or phenytoin (PHT), and in age-matched healthy males. Idiopathic generalized epilepsy (IGE) was diagnosed in 12 cases and partial epilepsy (PE) in 23 cases. Patients were seizure-free and did not show EEG abnormalities at repeated controls in the last 5 years, so that interfering effects of seizures were possibly excluded. The aim of the study was to evaluate both the role of epileptic syndromes and of anti-epileptic drugs on the endocrine function. Changes in sex hormone binding globulin, total and free testosterone, dihydrotestosterone and delta 4-androstenedione were found to be independent of the epileptic syndrome type. The LH response to LHRH was lower in PB-treated PE than in IGE subjects on the same drug regimen. An impairment of LH pulsatility with respect to controls was found in PE but not in IGE patients taking PB. Among antiepileptic drugs, PHT is associated with higher sex hormone binding globulin and estradiol and lower free testosterone and dihydrotestosterone levels. PB and CBZ, but not PHT, blunt the LH response to exogenous LHRH in PE. Prolactin responses to TRH were consistently enhanced in PE subjects treated with CBZ or PHT.

Urine melatonin in alcoholic patients: a marker of alcohol abuse?

Ethanol is known to alter central neurotransmission and endocrine functions. Urine melatonin was studied in 10 male chronic alcoholic patients, before and after two weeks of controlled alcohol abstinence, and in sex and age matched healthy controls. In both groups, 24-hour urines were collected in two fractions corresponding to day- (D) (08:00–20:00) and night- (N) (20:00–08:00) time. Urine melatonin was assayed by RIA after methylene chloride extraction. Twenty-four hour urine melatonin levels were calculated adding up D and N values. In patients during alcohol intake, the 24-hour urine melatonin levels were significantly higher than in controls (p=0.004, Student’s t test). A disruption of the physiological ratio between N and D values was also observed, since the higher melatonin levels occurred in the D fraction. In drinking alcoholics, melatonin D values were significantly higher than the D values found in controls (p < 0.01, Student’s t test) and in the same patients after alcohol withdrawal (p < 0.05). The N/D ratio approximated 1 during alcohol intake and became larger than 1 after alcohol withdrawal, as in the controls. The melatonin data were correlated with the suppressive effects of dexamethasone (DXT) on cortisol secretion evaluated both during alcohol intake and during abstinence. After alcohol withdrawal, the two (out of 10) patients, who remained unresponsive to the DXT suppression test, showed high D melatonin values and a low N/D ratio. These preliminary data indicate that in chronic alcoholism the pattern of urinary “melatonin- like immunoreactivity” is altered.

Circadian secretion of melatonin and thyrotropin in hospitalized aged patients.

Alterations in periodical functions are known to occur in aging and may be regarded as markers of the aging process itself. Melatonin and Thyroid Stimulating Hormone (TSH) circadian periodicities were studied in 22 aged subjects and in 13 adult controls. The study of rhythmicity was performed by the Cosinor analysis. Elderly subjects were hospitalized because of various concomitant diseases. Circadian periodicity of both hormones was disrupted in the aged group, and the deterioration of melatonin periodicity was significantly correlated with the decay in cognitive functions, quantified by the Mini Mental State evaluation. Diabetes was also found to affect, though not significantly, melatonin, but not TSH, periodicity. Melatonin and TSH nocturnal peaks were decreased in aged people. TSH oscillation amplitudes were inversely correlated with age. No correlation was found between melatonin and TSH secretory features both in adult and in aged subjects. (Aging Clin. Exp. Res. 5: 39–46, 1993)

Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone-releasing hormone on the pituitary-adrenal axis and on growth hormone secretion in dementia

Alterations of neuroendocrinological indices determined by the impaired regulating effects of cholinergic neurotransmission have been described in primary dementia. In this study we have evaluated the effects of acetylcholinesterase inhibition by pyridostigmine on growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7 patients with primary degenerative dementia and in 8 sex- and age-matched controls. Demented subjects showed higher cortisol basal levels and lower ACTH levels than controls. Pyridostigmine increased the GH response to GHRH in both groups, the effect being significantly enhanced in patients. An increase of ACTH and cortisol levels was found in both groups after pyridostigmine and CRH administration. Pyridostigmine pretreatment significantly increased the ACTH response to CRH in controls but not in patients. The obtained data may indicate that a muscarinic receptor upregulation and an impairment of somatostatinergic function are operative in the regulation of GH secretion in dementia. An underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the responses of ACTH and cortisol to CRH in this disorder.

Cholinergic Modulation of Growth Hormone-Releasing Hormone Effects on Growth Hormone Secretion in Dementia

An impairment of cholinergic and somatostatinergic neurotransmission have been reported in dementia. Both acetylcholine and somatostatin are involved in the regulation of growth hormone (GH) secretion. The effects of GH-releasing hormone (GHRH) 1-44 on GH release have been studied before and after the pretreatment with pyridostigmine or pirenzepine in subjects with senile dementia of the Alzheimer type, multi-infarct dementia and mixed dementia. The data have been compared with those obtained in an age-matched healthy control group. The GH response to GHRH is similar in the patients and in the controls, though the peak occurrence is significantly delayed in dementia. The cholinesterase inhibitor pyridostigmine enhances significantly the GH response to GHRH in both groups. The responses obtained in demented subjects are significantly larger than those found in the controls. Pirenzepine, a muscarinic receptor blocker, inhibits the GHRH effect on GH secretion in both groups. The findings may be interpreted in terms of an underlying impairment of the hypothalamic cholinergic neurotransmission, with an acetylcholine receptor supersensitivity that becomes apparent when the cholinergic tonus is enhanced by the inhibition of cholinesterase by pyridostigmine. No significant differences, due to the type of dementia, have been observed.

GROWTH HORMONE SECRETION IN PRIMARY DEGENERATIVE DEMENTIA: CORRELATIONS WITH COGNITIVE IMPAIRMENT

Changes in brain peptides and neurotransmitters are thought to elicit alterations of growth hormone (GH) secretion in dementia. Baseline GH levels and hormone responses to GH‐releasing hormone (GHRH)—administered alone or after pyridostigmine pretreatment—were evaluated in 17 patients, aged 52–83, with primary degenerative dementia quantified by the Clinical Dementia Rating (CDR) Scale and the Mini‐Mental State Examination (MMSE) with a view to detecting correlations between neuroendocrine and clinical data. Basal GH levels were not statistically different in patients and in age‐matched controls. However, when patients were split into the three CDR groups of disease severity, basal GH levels were significantly higher in those with more severe dementia than in all other patients and in controls. GH responses to GHRH, evaluated both in terms of peaks attained after simulation and of secretion areas under the curve (AUC), were significantly higher in patients than in controls after pyridostigmine pretreatment, but not after the infusion of GHRH alone. Patients with mild to moderate dementia had GH peaks after GHRH higher than more severe patients. Pyridostigmine did not potentiate GHRH effects in the more severe cases. The scores on Reys 15‐word test for memory function were directly correlated with GH peaks after GHRH. No correlations were found between GH data, age, body weight, disease duration and scores at other psychometric assessments such as MMSE, Ravens matrices, verbal fluency or WAIS tests.