18568
document
Estradiol and the addition of progesterone increase the sensitivity to a neurosteroid in postmenopausal women . The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid , pregnanolone , before and during different hormonal settings of postmenopausal hormone replacement therapy ( HRT ) , using natural progesterone . A second aim was to investigate whether the response to pregnanolone was associated with cyclicity in negative mood symptoms during treatment . Twenty six postmenopausal women with climacteric symptoms were administered HRT in a randomized , double blinded , placebo-controlled , crossover study . The women received 2 mg oral estradiol ( E ( 2 ) ) continuously during two 28-day cycles and 800 mg of vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle . Pharmacodynamic response to pregnanolone was assessed before treatment , and during the last week of each treatment cycle , by comparing the effects of intravenous pregnanolone ( 3alpha-hydroxy-5beta-pregnan-20-one ) on saccadic eye velocity ( SEV ) , saccade acceleration , saccade latency and self-rated sedation . Throughout the study daily symptom rating scales were kept . According to the daily symptom rating scales , patients were divided into two groups ; one group who displayed a significant variance in negative mood symptoms during HRT ( cyclicity ) and one group with no cyclical changes in negative mood symptoms during treatment . During treatment with either E ( 2 ) alone or E ( 2 ) +progesterone the response in saccadic eye movement parameters and in self-rated sedation to pregnanolone was enhanced compared to pretreatment values . The SEV , saccade acceleration and sedation responses to pregnanolone was also increased in women expressing cyclicity in negative mood symptoms compared to women with no cyclical changes in negative mood during HRT . In conclusion , during treatment with either E ( 2 ) alone , or E ( 2 ) +progesterone , pregnanolone sensitivity was increased . Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity during HRT .
18569
Intervention_Pharmacological
Estradiol
18570
Intervention_Pharmacological
progesterone
18571
Intervention_Pharmacological
neuroactive steroid , pregnanolone
18572
Intervention_Pharmacological
postmenopausal hormone replacement therapy ( HRT )
18573
Intervention_Pharmacological
natural progesterone
18574
Intervention_Pharmacological
pregnanolone
18575
Intervention_Pharmacological
HRT
18576
Intervention_Pharmacological
oral estradiol ( E ( 2 ) )
18577
Intervention_Pharmacological
vaginal progesterone
18578
Intervention_Control
placebo
18579
Intervention_Pharmacological
pregnanolone ( 3alpha-hydroxy-5beta-pregnan-20-one )
18580
Intervention_Pharmacological
HRT
18581
Intervention_Pharmacological
E ( 2 ) alone
18582
Intervention_Pharmacological
E ( 2 ) +progesterone
18583
Intervention_Pharmacological
pregnanolone
18584
Intervention_Pharmacological
HRT
18585
Intervention_Pharmacological
E ( 2 )
18586
Intervention_Pharmacological
E ( 2 ) +progesterone
18587
Intervention_Pharmacological
pregnanolone
18588
Intervention_Pharmacological
HRT
18589
Outcome_Mental
negative mood symptoms
18590
Outcome_Other
Pharmacodynamic response
18591
Outcome_Physical
saccadic eye velocity ( SEV ) , saccade acceleration , saccade latency and self-rated sedation
18592
Outcome_Mental
daily symptom rating scales
18593
Outcome_Mental
daily symptom rating scales
18594
Outcome_Mental
negative mood symptoms
18595
Outcome_Physical
saccadic eye movement parameters
18596
Outcome_Physical
self-rated sedation
18597
Outcome_Physical
saccade acceleration and sedation responses
18598
Outcome_Mental
negative mood symptoms
18599
Outcome_Physical
pregnanolone sensitivity
18600
Participant_Condition
postmenopausal
18601
Participant_Sex
women
18602
Participant_Sample-size
Twenty six
18603
Participant_Condition
postmenopausal
18604
Participant_Sex
women
18605
Participant_Condition
climacteric symptoms
18606
Participant_Condition
negative mood symptoms
18607
Participant_Condition
negative mood symptoms
18608
Participant_Condition
negative mood symptoms