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The effects of a single oral dose of phenobarbital (PB) on the 24 h secretion of prolactin, growth hormone and luteinizing hormone have been evaluated in normal women. An EEG record was taken and barbiturate levels assayed in serum. A statistically significant decrease of growth hormone 24 h mean levels was observed and growth hormone and prolactin values during sleep were diminished. No changes in luteinizing hormone concentrations were observed. After PB the EEG showed no important alterations in sleep pattern, but on the power analysis an increase above 16 Hz absolute power was detected during the waking period.

Endocrine changes have been reported in treated epileptic subjects, who often exhibit sexual dysfunctions, but the endocrine effects of single antiepileptic drugs have not been completely elucidated. In this study we have investigated the influence of phenobarbital (PB) on adenopituitary function and on peripheral sexual steroid pattern in 8 epileptic males. Chronic PB treatment does not modify luteinizing hormone (LH) pulsatile secretion. In the same subjects, LH and follicle stimulating hormone (FSH) response to Gonadotropin Releasing Hormone was blunted with respect to healthy controls both in terms of absolute values and of secretion areas. No difference was found in prolactin (PRL) response to Thyrotropin Releasing Hormone. In the epileptic group a significant increase in the levels of sex hormone binding globulin and a consequent decrease of the percent free testosterone have been observed. PB treatment also significantly lowers 17-beta-estradiol mean levels. These data suggest that PB independently affects both gonadotropin secretion and peripheral steroid pattern.

Summary: Circulating basal prolactin (PRL) levels were evaluated in 126 subjects of both sexes with partial or generalized epilepsy, who were treated with phenobarbital (PB) alone or in combination with either phenytoin or benzodiazepines. A significant increase in PRL levels was observed in male, but not in female, patients compared with a sex- and age-matched healthy volunteer group. Circadian PRL secretion, studied in six male epileptic patients on PB monotherapy and in nine normal subjects, showed comparable 24-h PRL mean values and a preserved PRL surge during the night in both groups; however, a statistically significant additional peak was found in male epileptic subjects during the late afternoon. The cosinor analysis of the data, used to evaluate PRL rhythmicity, showed a disruption of the 24-h periodicity in epileptic subjects, while the 12-h periodicity was maintained. These results indicate that central and/or peripheral mechanisms involved in PRL secretion control are more sensitive to PB alone or in combination with other antiepileptic drugs in male than in female subjects. However, the changes of PRL secretion we found were small and unrelated to the different clinical conditions. RESUME Les taux de prolactine basale circulante (PRL) ont ete mesures chez 126 sujets des deux sexes ayant une epilepsie, generalisee ou partielle, traitee par phenobarbital (PB) seul ou associea la phenytoine ou a des benzodiazepines. Une augmentation significative des taux de PRL a ete observee chez les hommes mais pas chez les femmes, par rapport a un roupe de volontaires sains apparies pour Page et pour le sexe. La secretion circadienne de PRL. etudiee chez 6 hommes epileptiques en monotherapie barbiturique et chez 6 sujets normaux, avait des valeurs moyennes comparables pendant les 24 H et le pic nocturne de PRL etait preserve dans les 2 groupes. Mais un pic supplementaire, statistiquement significatif a ete observe chez les hommes epileptiques pendant la fin de l'apres-midi. Une analyse COSINOR des donnees pour evaluer la rythmicite de la PRL a montre une rupture de la periodicite sur 24 H chez les sujets epileptiques, la periodicite sur 12 H etant maintenue. Ces resultats indiquent que les mecanismes centraux et/ou peripheriques impliques dans le controle de la secretion de PRL sont plus sensibles au PB, seul ou associea un autre antiepileptique, chez l'homme que chez la femme. Mais les modifications de secretion de PRL que nous avons trouvees sont faibles et ne sont pas en relation avec les diverses conditions cliniques. RESUMEN En 126 sujetos de ambos sexos con epilepsia parcial o generalizada, tratados con enobarbital (PB) como unica medicacion o asociado a fenitoina o a benzodiazepinas, se han valorado los niveles de prolactina basai circulante (PRL). Se ha observado, en los varones, un incremento significativo de los niveles de PRL pero no en las mujeres comparando estos resultados con los de un grupo de voluntarios sanos de edades y sexos comparables. La secrecion de PRL circadiana, estudiada en 6 enfermos epilepticos con monoterapia de PB, y en 9 sujetos normales, ha demostrado niveles medios de PRL comparables durante 24 horas, manteniendo invariable la descarga de PRL durante la noche en ambos grupos, pero se ha encontrado un pico adicional estadisticamente significativo en los epilepticos varones durante la tarde. El analisis de Cosinor de la informacion, llevado a cabo para valorar la ritmicidad de PRL, ha demostrado una alteracion de la periodicidad de 24 horas en sujetos epilepticos, mientras que se mantiene la periodicidad de 12 horas. Estos resultados indican que mecanismos centrales y/o perifericos, que parecen participar en el control de la secrecion de PRL, son mas sensibles al PB como medicacion unica o asociado a otros farmacos anticomiciales, en varones que en mujeres. Sin embargo, los cambios de secrecion de PRL son mas reducidos y no tienen relacion con situaciones clinicas diferentes.

Prolactin (PRL) responses to dopamine (DA) blockers and to direct and indirect DA agonists have been studied in 23 healthy women, 17 women with catamenial migraine and 17 with non-catamenial migraine in both their follicular and luteal phases. PRL responses to the DA blockers were greater in the follicular phase of both migraine groups than in controls. The inhibitory effect of nomifensine on PRL secretion was dampened in the follicular phase of both migraine groups. These findings demonstrate an increased PRL reserve in migraine and suggest the existence of a dopaminergic supersensitivity of the lactotrophic postsynaptic DA receptors. The impaired inhibitory effect of nomifensine on PRL secretion hints at a decrease of the presynaptic DA content in tuberoinfundibular DA neurons. In migrainous women 17-β-oestradiol levels are higher in both ovarian phases, whereas progesterone concentrations and the progesterone to oestradiol ratio are lower than in healthy subjects in the luteal phase. These data suggest the existence of a change in the oestrogen-dependent modulation of pituitary DA receptors.

The effect of benserazide administration on the secretion of GH, PRL, and TSH has been considered as an index of dopamine regulatory actions. Nine acromegalic patients and nine normal subjects were given a sngle 125 mg oral dose of benserazide, and serum GH, PRL, and TSH were determined by RIA methods every 30 min for 4 h. Benserazide did not alter GH values either in normal subjects or in acromegalic patients. A significant increase of serum PRL was found in both groups, and the increase was similar in normoprolactinemic and in hyperprolactinemic acromegalic patients. A significant increase in TSH levels was found only in acromegalic patients. Thus, a decrease in dopamine outside the blood-brain barrier did not affect GH secretion, whereas PRL secretion was changed in the acromegalic as well as in the control group.