Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone.
BACKGROUND
Allopregnanolone effects on mood in postmenopausal women are unclear thus far.


OBJECTIVE
Allopregnanolone is a neuroactive steroid with contradictory effects. Anaesthetic, sedative, and anxiolytic as well as aggressive and anxiogenic properties have been reported. The aim of this study is to compare severity of negative mood between women receiving different serum allopregnanolone concentrations during progesterone treatment.


METHODS
A randomized, placebo-controlled, double-blind, crossover study of postmenopausal women (n=43) treated with 2 mg estradiol daily during four treatment cycles. Oral micronized progesterone at 30, 60, and 200 mg/day, and placebo were added sequentially to each cycle. Participants kept daily symptom ratings using a validated rating scale. Blood samples for progesterone and allopregnanolone analyses were collected during each treatment cycle.


RESULTS
During progesterone treatment, women had significantly higher negative mood scores when allopregnanolone serum concentration was in the range of 1.5-2 nmol/l compared to lower and higher concentrations. In addition, women displayed a significant increase in negative mood during the progesterone treatment period, compared to the estradiol-only period when 30 mg progesterone daily was used. On the other hand, treatment with higher doses of progesterone had no influence on negative mood.


CONCLUSIONS
Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.
Andréen
Lotta
L
Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics and Gynecology, Norrlands University Hospital, SE-901 85, Umeå, Sweden.
Sundström-Poromaa
Inger
I
Bixo
Marie
M
Nyberg
Sigrid
S
Bäckström
Torbjörn
T
D000284:Administration, Oral; D000339:Affect / Q000187:drug effects*; D002979:Climacteric / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000097:blood / Q000494:pharmacology*; D008875:Middle Aged; D011280:Pregnanolone / Q000097:blood*
D004958:Estradiol; D011280:Pregnanolone; D017258:Medroxyprogesterone Acetate