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Psychoneuroendocrine Aspects of Temporolimbic Epilepsy Many reproductive steroids have neuroactive effects that can modulate neuronal excitability andinfluence emotions. Emotional disorders may result when 1) abnormal endocrine states interactwith normal brain, 2) normal endocrine states interact with abnormal brain, and 3) abnormalendocrine states interact with abnormal brain. An understanding of these pathogenetic relation-ships and the potential therapeutic role of reproductive hormones should lead to a more effectiveand comprehensive management of women and men with anxiety and mood disorders. recurrent states of deepened or exaggerated affect and theassociation of perception with exaggerated emotional and Conceptualizations of mind have shifted from intangible motivational significance.6 The resulting deepened emo- to tangible. Based on the results of experimental animal tional state may represent or contribute to at least some of and clinical brain ablation and stimulation investigations, the altered mood, personality, and behavior characteristics many mental attributes that were previously ascribed to a that are commonly known as the interictal features of tem- soul or spiritual entity are now commonly referred to the poral lobe epilepsy (temporolimbic epilepsy, TLE).9 This brain. Attention, memory, perception, language, cognition, syndrome includes intense affect, anxiety, depression, an- judgment, emotions, and behavior are considered to be ger, rage, humorless sobriety, elation, feelings of personal functions that can be ascribed to the activity of 1) discrete destiny or grandiosity, obsessionalism, guilt, hypermoral- brain areas, 2) systems of interconnected brain areas, and ism, religiosity, philosophical interests, hypergraphia, par- 3) parallel processing in brain systems.1–5 Altered or dis- anoid ideation, circumstantiality, tangentiality, viscosity, ordered mental processes result from dysfunction or dis- dependence, and altered sexual drives.
connection of brain areas or systems.1–5 Altered mood and interictal personality features can Altered or disordered mental processes may also occur cause functional impairment and distress in perhaps 30– as a result of “sensory-limbic hyperconnectivity,” that is, 50% of women and men with TLE.10,11 Although these the association of perceptions with exaggerated emotional disorders may respond favorably to antiseizure medica- and motivational significance due to excessive limbic ac- tions,10 treatment is often unsuccessful despite the achieve- tivity in the context of epilepsy.6 Medial temporal lobe ment of good seizure control.3 In some cases, worsening structures, especially the amygdala and hippocampus, are may occur.3 This lack of success may be due to the fact usually the sites of origin, or at least involvement, of epi-leptogenic discharges in partial seizures.7 These regions Received April 2, 1998; revised August 28, 1998; accepted September form the part of the limbic system where emotions are 10, 1998. From Harvard Neuroendocrine Unit, Beth Israel DeaconessMedical Center, Department of Neurology, Harvard Medical School. Ad- thought to have representation.3,8 Excessive activation of dress reprint requests to Dr. Herzog, Beth Israel Hospital, 330 Brookline these regions by epileptogenic discharges can lead to sei- zures. Excessive activation may also lead to persistent or Copyright ᭧ 1999 The Academy of Psychosomatic Medicine.
that antiseizure medications typically act to prevent the Daily progesterone using 200 mg lozenges tid during the spread of seizure discharges, but generally do not eliminate second half of each cycle on Days 14–25 with subsequent grad-ual tapering and discontinuation of therapy over 4 days allevi- the epileptogenic focus or restore entirely normal physio- ated anxiety and staring episodes, as well as menstrually related logic function to the involved area, as evidenced by inter- exacerbations of agitated depression and psychosis. She re- ictal electroencephalogram (EEG), single photon emission quired no further hospitalizations during the entire following computed tomography (SPECT), and positron emission to- mography (PET) data.12 Antiepileptic drugs, moreover, Comment: The syndrome of disabling mood changes and
psychosis in relation to menses has been termed cyclic or peri- may activate inhibitory mechanisms that could contribute odic psychosis.15,16 The psychosis is characterized by increasing to cognitive deficits and emotional changes.10,11,13 psychomotor excitement for 7–14 days prior to menstruation,followed by psychomotor retardation during menstruation.15 It is commonly associated with temporal lobe EEG abnormali- ties15,17 and other markers of anomalous brain substrates.17 Symptoms have been related to excessive estradiol18 or dimin-ished progesterone15,19 influence on the brain. ECT and psycho-tropic medications are often of limited value.15 Cyclic psycho- Agitated depression and anxiety disorders including anxi- sis has been effectively treated by various forms of oral and ety, panic attacks, phobias, and obsessive compulsive dis- parenteral reproductive hormones that eliminate menses, reduce order are frequent concomitants of TLE9,13,14 that often estrogenic effects, or increase progestin levels.17,20–22 In the show catamenial (i.e., menstrual cycle–related) patterns of case of Ms. B., substantial improvement occurred with the cy- exacerbation and favorable response to hormonal treatment clic use of progesterone and was contingent on a gradual taperof progesterone premenstrually.
with progesterone or clomiphene. These points are illus-trated by the following cases.
Ms. F. is a 31-year-old woman with irregular cycles and infer-tility, who, beginning in the second month of attempted ovula- Ms. B. is a 29-year-old woman with depression, considered to tion induction with chorionic gonadotropin, developed severe be bipolar illness, dating back to her teens. For about 2 weeks panic attacks with a type-3 pattern of catamenial exacerbation.
before each menstrual period, she would become progressively She also experienced milder daily symptoms of fear, sweatiness more irritable, depressed, angry, argumentative, and aggressive.
of her palms, palpitations, nausea, and occasionally terrible foul She would stay in her house, overeat and feel panicky, nervous, and sometimes suicidal. As menstruation approached, confu- Ms. F. was the product of an almost 10-month gestation sion, paranoid ideation, and other delusions developed, often to with very difficult labor and forceps delivery. Her father and the point of frank psychosis. These symptoms improved dra- sister were left handed. Her mother developed seizures as an matically on Day 2 of each cycle. Severity of her symptoms in- creased progressively over the years. Lithium exacerbated her Ms. F. had abnormally heightened deep tendon reflexes.
confusion. Tricyclics increased the severity of the cycling. Ol- Her EEG showed paroxysmal epileptiform discharges in both factory and gustatory hallucinations, as well as premenstrual temporal regions. During the hyperventilation phase of her episodes of staring and unresponsiveness, raised the possibility EEG, she experienced a very high level of anxiety, fear, cold of a seizure disorder. EEG showed epileptiform discharges and sweats, rapid heart rate, and breathing difficulty. A CT scan of paroxysmal slowing over the left temporal region. Her daily medications, carbamazepine (1,400 mg) and clonazepam (5 Ms. F.’s symptoms were refractory to antiepileptic drugs mg), lessened her lapses but did not benefit the cyclic emo- and benzodiazepines. The addition of progesterone (200 mg tid) tional deterioration that eventually required monthly hospitali- during the second half of each cycle eliminated her severe at- zation for psychosis and suicidal threats nor her staring epi- tacks entirely and permitted her to return to her full-time occu- Ms. B.’s past medical history was remarkable for learning Comment: Concomitant panic attacks and paroxysmal
difficulties as a child, a concussion during adolescence, irregu- temporal lobe EEG abnormalities are now well recorded in the lar menstrual cycles, and hirsutism. The family history was re- medical literature.23–28 Symptoms and manifestations of fear markable for major mood disorder affecting her brother and and anxiety are among the commonest auras of TLE.3 They both parents. Her mother was left handed.
may also occur, however, in the setting of EEG abnormalities On examination, she had a right hemihypoplasia and a alone, that is, in the total or relative absence of other clinical vascular birthmark over the dorsal right forearm.
seizure manifestations, sometimes known as atypical panic at- tacks.27 A causal relationship between epilepsy and panic at- gesterone resulted in the occurrence of seizures and extremely tacks has been suggested in some cases by the demonstration of severe agitated depression during the estrogen phase. Treatment a temporal association between the occurrence of paroxysmal with natural progesterone alone during the second half of each temporal lobe EEG discharges and panic attacks.28 In Weilburg cycle, however, was associated with the elimination of psycho- and associates’ series, EEG telemetry demonstrated focal parox- sis and overt seizures, a dramatic stabilization of her mood, a ysmal EEG changes in 45% of subjects who had captured at- marked lessening in her obsessive thoughts and compulsive rit- tacks. The effective use of progesterone in management has not uals, and the elimination of paranoid features. Attempts to stop her progesterone treatment were associated with florid recur-rences of symptoms.
Case 3. Depression and Obsessive-Compulsive Disorder Case 4. Obsessive-Compulsive Disorder and Panic Attacks Ms. G. is a 23-year-old woman who had cyclic exacerbation ofher major unipolar depressive mood disorder and obsessive- Ms. P., a 31-year-old left-handed woman, was referred for eval- compulsive disorder (OCD) in relation to her menstrual cycle.
uation of OCD, panic attacks, and phobias that developed 5 Irritability developed in the second week. Angry thoughts with years earlier, 3 months after the birth of her daughter. Her episodic rage became progressively more prominent after Day symptoms were much more severe in the second half of each 14. During the third week, malicious intent was perceived in menstrual cycle, especially premenstrually. Hypochondriacal everyone around her. She became confused, hyper-religious, traits were noted as early as 5 years of age. She had anorexia read the Bible constantly and smelled unpleasant things. Her and amenorrhea as a teen and later developed infrequent epi- generally intermittent and minor obsessions about religious and sodes of confusion and incoherent speech without subsequent moralistic themes became constant and overwhelming. They recollection. Cycles always had irregular intervals ranging be- reached the point that she would continuously feel a great need tween 24 and 36 days. Her brother was hospitalized on two oc- to confess. Ms. G. carried out rituals all day, organizing reli- casions for depression, obsessive-compulsive behavior, and hy- gious materials around her room. These activities helped to pochondriacal traits. Depression affected a number of family control her high level of anxiety. Recurrent thoughts about cut- members on her father’s side. A maternal grandfather was left ting her wrists with a knife kept her from sleep at night. These thoughts and rituals remained prominent during the fourth week On exam, there was a notable skeletal asymmetry with the along with agitation, depression, emotional lability, and para- left hand being larger than the right, decreased smell perception noid ideation. By the second day of menstruation, she felt much on the right side, and a mild speech articulation disturbance.
The EEG showed paroxysmal epileptiform temporal lobe dis- The symptoms had their onset in adolescence and became charges, predominating on the right side.
progressively more pervasive and severe during adolescence Trials of tricyclic and monoamine oxidase inhibitor and her early twenties. They necessitated repeated hospitaliza- (MAOI) antidepressants during her twenties did not agree with tions for psychosis and suicide attempts, generally in the fourth her. Her mood responded well to carbamazepine and her cycle week of each cycle. At the time of referral, she was spending became regulated for the first time. While on carbamazepine, more time in the hospital than at home.
she became pregnant. This occurred despite several years of in- Her past medical history was remarkable for perinatal an- fertility. She did very well during the pregnancy and delivery.
oxia and irregular cycles with menometrorrhagia and prolonged Within 3 months after delivery, however, her obsessive and menstrual intervals of about 40 days. Fluid retention up to 10 compulsive symptoms developed and increased to a disabling or 15 lbs and breast tenderness were prominent premenstrually.
level despite psychotherapy and carbamazepine. A second preg- She had excessive hair growth but no galactorrhea. Pelvic ultra- nancy 4 years later was again associated with a marked im- sound showed multiple ovarian cysts. Major mood disorder and provement in her symptoms. She elected not to breastfeed her left handedness were prominent on both sides of her family.
baby. She had moderately severe postpartum depression. This Her mother had a history of irregular menstrual cycles and was replaced after 1 month by anxiety, agitation, panic attacks, phobias, obsessions, and compulsive behavior, which became Medications were ineffective including monoamine oxi- progressively more severe and pervasive. Three months after dase inhibitors, methylphenidate, haloperidol, prolixin, lithium, delivery and endocrine documentation of inadequate luteal and ECT. Desipramine and amitriptyline increased her cycling.
phase cycles, progesterone therapy was started using 200 mg She had a major motor seizure while on fluoxetine and also fol- lozenges three times daily on Days 14–25 of each cycle fol- lowing ECT. The possibility of TLE was raised. EEG showed lowed by tapering and discontinuation by Day 28. During the paroxysmal left temporal (sphenoidal) sharp and slow activity.
next 6 months, she had regular cycles. She felt relaxed. Panic Subsequent EEGs showed independent bitemporal paroxysmal attacks were eliminated and OCD features were described as a epileptiform activity in one of four studies.
lot better by the patient, her husband, and her therapist. Proges- She improved marginally with antiepileptic drugs. An at- terone was discontinued. Her cycle then became irregular with tempt to cycle her with conjugated estrogen and medroxypro- periods occurring every 2–3 weeks. She experienced, moreover, a recurrence of panic attacks, severe worsening of obsessions, depressed, obsessed about premenstrual syndrome, and had rituals and phobias, and episodes of incoherence without recol- only 5/30 “good days” per month.
lection of events. Re-institution of progesterone regulated her Comment: Ms. D.’s history of oligomenorrhea, hirsutism,
cycle and markedly benefited her symptoms again.
and ovarian cysts was diagnostic of PCO. PCO is commonly Comment: Manifestations of OCD are common features
associated with TLE, depression, and migraine.47,48 The anovu- of interictal personality among individuals who have temporal latory cycles of PCO expose temporal lobe limbic structures to lobe seizures.6 They may also occur, as in Ms. G. and Ms. P., in a constant estrogen effect without normal luteal phase eleva- the setting of temporal epileptiform discharges without promi- tions of progesterone and thereby heighten seizure activity and nent evidence of seizures, show catamenial patterns of exacer- likely contribute to agitated depression and mood instability.
bation, and respond favorably to progesterone therapy.29 Clomiphene therapy corrects the endocrine abnormalities of A reproductive hormonal influence on OCD manifestations PCO, normalizes the menstrual cycle, and lessens seizure dis- is consistent with popular structural and chemical neurological charges.18 Normalization of the menstrual cycle and luteal hypotheses of etiology and pathogenesis. As of yet, there is no phase progesterone secretion generally also benefits the catame- established basis for OCD. It is frequently reported to occur, nial exacerbation of agitated depression and OCD in the setting however, in the setting of neurological disorders, in particular, those that involve the limbic system or basal ganglia. These in-clude, for example, temporolimbic epilepsy,6,9 encephalitis leth-argica,30–35 Sydenham’s chorea,36,37 Tourette syndrome,38 tu-mors in the region of the cingulate gyrus, and lesions of the Case 6. Cumulative Hormonal Effects on caudate nucleus.39,40 Cingulotomy, moreover, has been reported to benefit patients.41–44 This distribution of lesions is relevantbecause the neuronal activity of the basal ganglia, like the lim-bic system, are modulated by gonadal steroids.45,46 Ms. S., a 36-year-old left-handed woman with prenatal diethyl-stilbesterol (DES) exposure, presented with severe anxiety,widely fluctuating moods, and intermittent psychosis. She hadbeen very well until 2 years earlier when she required a totalhysterectomy and bilateral oophorectomy for an infection that Case 5. Polycystic Ovarian Syndrome and Depression she acquired during tests for infertility. She did well on conju-gated estrogen (0.625 mg daily for 3 months). Subsequently,however, Ms. S. began to develop increasing amounts of anxi- Ms. D., a 40-year-old wife, mother, and gospel singer, came to ety, agitation, irritability, and mood lability. Her anxiety, at see me because she felt that she had exhausted local medical times, would build to levels where she would physically shake, resources and felt hopeless. She had polycystic ovarian syn- experience palpitations, and become only loosely tied to reality.
drome (oligomenorrhea, hirsutism, ultrasound demonstration of Over the course of 2 years she was seen by several psychiatrists multiple follicular cysts, and increased ovarian stroma), irritable and was variably labeled as having a major mood disorder or bowel syndrome, personality disorder, OCD, agoraphobia, and anxiety disorder. Minor tranquilizers produced excessive seda- depression. She had been refractory to a large number of anti- tion and depression with regular use. Antidepressants increased depressant and anxiolytic drugs and experienced little improve- her agitation. Major tranquilizers were poorly tolerated. Discon- ment while attending psychiatry, allergy, and premenstrual clin- tinuation of estrogen replacement left her depressed and with- ics. An EEG, prompted by the episodic nature of her out energy. Increased estrogen dosage aggravated her anxiety.
symptoms, showed paroxysmal sharp and slow waves in the As a child, Ms. S. walked late, between 2 and 3 years of left frontotemporal region. Carbamazepine provided significant age, and required elocution lessons for articulation difficulties.
relief from her usual episodes, lasting minutes to hours, of “un- She had green eyes and blonde hair, a short stature, just under 5 reality,” “black depression,” and “uncontrollable crying.” She feet in height, and a notable skeletal asymmetry with the right was once again able to sing masses at local churches. However, foot being between one-half to one shoe size bigger. There she continued to have fears and obsessions. Her menstrual pe- were no elementary neurological findings aside from the above- riods were very irregular, and basal body temperature charts mentioned minimal dysarthria. She was agitated and labile. An gave no indication of ovulation. For the next 3 months, she EEG showed bitemporal paroxysmal sharp waves and slowing, took clomiphene (50 mg daily) on Days 5–9 of her menstrual cycle and enjoyed a period of unparalleled well-being. She had Discontinuation of estrogen produced a rapid, dramatic re- no further episodic symptoms. She lost her fears and obses- duction in anxiety and agitation. After 3 days of feeling well sions. She was able to perform at local churches. She chose, off estrogen, however, she developed rapidly increasing asthe- however, to stop doing this. She had an extramarital “affair” nia. She could not get out of bed and felt hopelessly depressed.
and kept a chart that showed 20/30 “good days” per month.
The reintroduction of conjugated estrogen resulted in marked The clomiphene was stopped in mid-October because of an epi- improvement within hours. She became animated and lively.
sode of severe pelvic pain. Subsequently, she continued to ovu- After 4 days of therapy, however, she became racy, agitated, late regularly for 2 months, but in December, January, and Feb- panicked, disorganized, and very concerned about “losing her ruary she once again developed irregular cycles, became mind.” Progesterone lozenges (100 mg tid) were added. After 1 hour, she became calm and organized. She did very well for 4 function. Moreover, testosterone has not lessened seizures days. By the 5th day, however, she once again could not get out despite some reports of its anticonvulsant properties in ex- of bed and felt asthenic and hopeless. Both hormones were dis- perimental animals.56 One possible explanation is that an- continued with resulting improvement for 2 days, followed byrecurrence of low energy and mood. At this point, she was tiepileptic drugs that induce increased enzyme synthesis placed on a cyclic 10-day regimen of estrogen for 4 days, estro- may enhance the conversion of testosterone to estradiol by gen plus progesterone for the next 4 days, and then no hormone aromatase.57 Estradiol lowers male sexual interest and for 2 days. On this unusual 10-day cycle, she has done very function58 and increases seizure discharges59,60 and anxi- well. She has been able to establish a new business and return ety. The addition of testolactone (300–500 mg daily), an Comment: Hormonal effects on emotional behavior are
aromatase inhibitor, and depotestosterone (400 mg bi- often exaggerated in the setting of abnormal or anomalous tem- weekly) to baseline antiepileptic drug therapy produced porolimbic substrates.17,19 Hormones, however, can also have a clinically and statistically significantly better effects on progressive, cumulatively increasing effect on behavior. Ms. S.
sexual interest and function as well as on seizure frequency presents an extreme example of this phenomenon. Both typesof responses are especially notable in the setting of temporolim- and anxiety than treatment adding testosterone alone.55 bic epileptiform discharges, as in this case.19 These effects may This is illustrated in a 52-year-old hypogonadal man with represent progressively increasing neuronal sensitivity and reac- intractable seizures on baseline carbamazepine therapy tivity to continuous hormonal exposure. Two mechanisms may (Table 1).61 A possible anxiogenic effect of estradiol in be involved: 1) estradiol can progressively increase dendritic men as well as women is supported by the apparent asso- branching and surface excitatory synapses,49 as well as its ownspecific cytoplasmic receptors;50 2) the epileptogenic influence ciation between estradiol and anxiety levels as indicated by of estradiol exerts a kindling effect over time on limbic struc- anxiety scores in the Profile of Mood States.
tures.51 Estrogen effects are limited in both instances by proges-terone. Progesterone reduces dendritic branching and excitatory synapses,49 as well as the number of estradiol receptors.52 Italso inhibits kindling and epileptiform activity.53 In the case ofMs. S., the energizing effects of estrogen became pathologically Clomiphene dramatically benefited sexual interest, po- exaggerated after a few days of exposure, leading to anxiety tency, and seizure control in one case report of a man with and agitation. The sedating effects of progesterone effectively complex partial seizures and hypogonadotropic hypogon- resolved the situation acutely but, after a few days, produced adism.62 Seizures were eliminated during clomiphene use exaggerated effects of its own. The build up of both types ofundesirable effects was prevented by a short cycle.
in another case with epilepsy and oligospermia.63 It offeredno benefit, however, for a man who had complex partial seizures and hypergonadotropic hypogonadism, that is go- nadal failure.62 Total and free antiseizure medication levels were not affected. The mechanism of clomiphene actionon seizure activity is conjectural but may involve either the normalization of the serum testosterone level or direct an- Testosterone replacement is the most common form of tiestrogenic effects on epileptogenic limbic structures that therapy for sexual dysfunction resulting from hypogonad- have high-density estradiol receptors. An effect of clomi- ism. Its efficacy in men with epilepsy, however, is not phene on sexual interest and function as well as competi- proven. In our experience with 12 men who had diminished tive drive is suggested by the following case.
sexual interest and reduced potency in the setting of TLEand antiepileptic drug use, biweekly 400-mg im injectionsof depotestosterone enanthate were associated with nor- malization of serum free testosterone levels and moderate improvement in sexual interest and potency scores in all12 men. Seizure frequency showed no significantchange.54,55 Mr. W., a 36-year-old man with left-sided sensorimotor andsecondary generalized seizures of 16 years’ duration, was re- ferred for evaluation of refractory epilepsy and infertility. His treatment regimen consisted of carbamazepine (200 mg fivetimes daily) and primidone (250 mg four times daily). Neuro- Testosterone therapy in our experience has been only logical examinations were remarkable for variable mild left moderately effective in restoring reproductive and sexual hemiparesis. EEGs were mildly abnormal because of bilateral paroxysmal temporal theta slowing. A pneumoencephalogram dihydrotestosterone, which blocks NMDA-type glutamate showed dilation of the right temporal horn. His personality transmission and may be responsible for antiseizure effects.
showed great depth of feeling, excessive attention to detail, un- Testosterone has energizing effects and increases sexual assertive, placid demeanor, and diminished sexual interest. Forseveral years, he had reproductive dysfunction consisting of in- desire in both men and women. In excess, however, it sufficient erection for penetration and no ejaculation. The sex- may promote aggressive, impulsive, and hypersexual be- ual and reproductive dysfunction seriously threatened his mari- tal life. External genitalia and testicular ultrasound were Temporolimbic dysfunction can produce altered hy- pothalamopituitary regulation of gonadal steroid secretion, Reproductive endocrine profile showed decreased serum luteinizing hormone and testosterone. Semen analysis in 1986 which can lead to abnormal hormonal influences on emo- showed a normal sperm count but decreased motility values.
tional behavior. Hormonal effects, moreover, tend to be After 1 month on 25 mg of clomiphene daily, the patient and exaggerated or idiosyncratic in the setting of an abnormal his wife reported that he demonstrated a more assertive attitude, or anomalous temporolimbic substrate, especially tempo- competitive drive, and increased sexual desire. He could rolimbic epilepsy. In this particular setting, hormones can achieve sexually functional erections. His luteinizing hormoneand testosterone levels normalized. She became pregnant after 3 also have a progressive, cumulatively increasing effect on months and delivered a healthy baby boy after 9 months. He emotional behavior, such that the normal physiological remained on clomiphene therapy for a total of 6 months. Dur- emotional effect of a hormone becomes transformed over ing the entire treatment period, he had no seizures. After clomi- days or weeks of continuous unopposed exposure, into a phene was discontinued, seizures recurred on a weekly basis pathological emotional state. This may reflect progres- and he resumed his more unassertive, placid, hyposexual de- sively increasing or kindled neuronal responsivity to con- tinuous hormonal exposure perhaps by virtue of changes in the number of dendritic spines and receptors. Finally,there is reason to believe that repeated episodes of psycho- The temporolimbic structures of the brain that subserve socially triggered emotional stress may utilize the limbic emotional representation are highly epileptogenic and play kindling paradigm to promote more spontaneously occur- an important role in the modulation of hormonal secretion ring recurrent mood and anxiety disorders. Such a kindling and mediation of hormonal feedback. Estrogen is highly process could also play an important role in the frequent epileptogenic and exerts energizing and antidepressant ef- association of reproductive dysfunction with anxiety and fects. Excessive estrogen influence produces anxiety, agi- mood disorders in both men and women.
tation, irritability, and lability. It can promote the devel- Emotional disorders may result when abnormal en- opment of anxiety manifestations (e.g., panic, phobias, and docrine states interact with normal brain, when normal en- obsessive-compulsive disorder). Progesterone and its me- docrine states interact with abnormal brain, and when ab- tabolites inhibit kindling and seizure activity. They have normal endocrine states interact with abnormal brain. An potent anxiolytic effects, possibly by virtue of their GA- understanding of these relationships and the therapeutic BAergic activity. Excessive progesterone influence pro- role of reproductive hormones should lead to a more ef- duces sedation and depression. Testosterone has two major fective and comprehensive management of women and metabolites: estradiol, which can exacerbate seizures, and men with anxiety and mood disorders.
Testosterone versus testosterone-testolactone effects on sexual interest, potency, and seizure frequency
Sexual Function (score/20)
Seizures per week
Testosterone (ng/ml)
E2 (pg/ml)
Anxiety (score/32)
*Abnormal value.
Note: Sexual function: score on standardized inventory of sexual interest and potency. Anxiety: score on anxiety scale of Profiles of Mood States.
References
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