Effects of Long‐Term Antiepileptic Therapy on the Hypothalamic‐Pituitary Axis in Man

Franceschi, M.; Perego, L.; Cavagnini, Francesco; Cattaneo, A.; Invitti, Cecilia; Caviezel, F; Ferini‐Strambi, Luigi; Smirne, Salvatore

doi:10.1111/j.1528-1157.1984.tb04154.x

Cited by 79 publications

(37 citation statements)

References 14 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, a direct, inhibitory effect of AED treatment on 17a-hydroxyprogesterone synthesis in the adrenal cortex might explain our finding. Serum cortisol concentrations remained unchanged in both the men and women with epilepsy, a finding which is in accordance with those of other investigators (26,42).…”

Section: B Stoffel-wagner Et a Tsupporting

confidence: 82%

Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication

et al. 1998

View full text Add to dashboard Cite

Summary: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 17a-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, follicularphase LH, and luteal-phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17a-hydroxyprogesterone, free testosterone, inhibin B, and the testosteroneLH 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 testosteroneLH 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 17a-hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.

show abstract

Section: B Stoffel-wagner Et a Tsupporting

confidence: 82%

Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication

et al. 1998

View full text Add to dashboard Cite

show abstract

“…In contrast, phenobarbital treatment seemed to have no effect on the normal growth hormone plasma profiles secreted by adult control rats neonatally exposed to saline [20]. Relevant to these animal studies are clinical findings demonstrating that in utero exposure to phenobarbital [36] as well as long-term phenobarbital anticonvulsant therapy [37] can reduce the pulse amplitudes of plasma growth hormone in humans.…”

Section: Discussionmentioning

confidence: 99%

Phenobarbital-Imprinted Overinduction of Adult Constituent CYP Isoforms

Agrawal¹,

Shapiro²

2003

Pharmacology

View full text Add to dashboard Cite

Newborn male and female rats were treated with therapeutic-like levels of phenobarbital to determine whether early exposure to the barbiturate permanently alters (i.e., imprints) mechanisms regulating induction of constituent CYP (cytochrome P-450) isoforms. When the rats were 65 and 150 days old, they were rechallenged with phenobarbital at doses reflecting either the possible inducing activities of environmental agents (1 mg/kg) or at the minimal anticonvulsant therapeutic dose for the rat (10 mg/kg). The expression levels (mRNA and protein) of constituent, gender-dependent CYP2C6, CYP2C7, CYP2C11, CYP2C12, CYP2C13, and CYP3A2 and nonconstitutive CYP3A1 were monitored at various times (i.e., 0.1–136 h) during the rechallenge period. The major female-specific CYP2C12 and male-specific CYP2C13 were unresponsive to induction, whereas the major male-specific CYP2C11 responded to phenobarbital administration with a 100% increase in transcript levels that were not translated into new protein. The expression of the other isoforms was significantly elevated by both doses of phenobarbital (10 mg >1 mg), though CYP2C6, CYP3A1, and CYP3A2 levels were increased an additional 30–50% when the animals were neonatally exposed to the barbiturate, demonstrating for the first time that mechanisms regulating induction of constitutive CYPs in adults are imprintable at birth. This overinduction response appears to result, at least in part, from phenobarbital-programmed alterations in the sexually dimorphic plasma growth hormone profiles that normally regulate expression of the isoforms. The long-term health consequences of the overinduction response and possible clinical significance are discussed.

show abstract

“…Prolactin is known to rise in sleep (20) (when most cases of SUDEP occur) and with some AEDs (21)(22)(23)(24)(25)(26)(27)(28). Although it is possible that the increase in prolactin in three patients, in whom there was no clinical evidence of a seizure, might have been caused by sleep-related increase (29), overall these factors do not seem to have had much effect on prolactin measurements in the SUDEP and the control groups with epilepsy.…”

Section: Discussionmentioning

confidence: 89%

Prolactin Levels in Sudden Unexpected Death in Epilepsy

Opeskin

Clarke²,

Berkovic

2000

Epilepsia

View full text Add to dashboard Cite

- Summary:Purpose: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure.Methods: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy.The majority of sudden unexpected deaths in epilepsy (SUDEP) are unwitnessed, and in the absence of a better explanation, death is believed to be the result of a seizure. Clinical evidence for terminal seizure is found in up to about a third of cases (1-5), but whether seizures (either witnessed or unwitnessed) always precede SU-DEP is unknown.Serum prolactin has been observed to increase after generalized tonicklonic seizures (6-10) and complex partial seizures (8,ll-16), and the mechanism by which seizures are proposed to cause prolactin elevation involves propagation of the electrical discharge to the hypothalamus, thereby influencing prolactin release (16). Generally serum prolactin does not rise after simple partial or pseudoseizures (8,9,15,17,18 Results: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects.Conclusions: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15-20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure. Key Words: Prolactin-Epilepsy-Sudden unexpected death.The purpose of this study was to examine prolactin levels in SUDEP and control groups. If prolactin was consistently increased in SUDEP cases, but not in controls, then we would infer that terminal seizui-es had occurred in the SUDEP group.

show abstract

Effects of Long‐Term Antiepileptic Therapy on the Hypothalamic‐Pituitary Axis in Man

Cited by 79 publications

References 14 publications

Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication

Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication

Phenobarbital-Imprinted Overinduction of Adult Constituent CYP Isoforms

Prolactin Levels in Sudden Unexpected Death in Epilepsy

Contact Info

Product

Resources

About