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Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
Vise andre og tillknytning
2006 (engelsk)Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 54, nr 3, s. 238-244Artikkel i tidsskrift (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
2006. Vol. 54, nr 3, s. 238-244
Emneord [en]
Administration; Oral, Adult, Aged, Area Under Curve, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Postmenopause, Pregnanolone/administration & dosage/blood/pharmacokinetics, Progesterone/administration & dosage/blood/*pharmacokinetics
Identifikatorer
URN: urn:nbn:se:umu:diva-10381DOI: 10.1016/j.maturitas.2005.11.005PubMedID: 16406399OAI: oai:DiVA.org:umu-10381DiVA, id: diva2:150052
Tilgjengelig fra: 2008-09-02 Laget: 2008-09-02 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Inngår i avhandling
1. Allopregnanolone and mood: studies of postmenopausal women during treatment with progesterone
Åpne denne publikasjonen i ny fane eller vindu >>Allopregnanolone and mood: studies of postmenopausal women during treatment with progesterone
2006 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Introduction. Allopregnanolone and pregnanolone (neuroactive metabolites of progesterone) act as positive modulators of the GABAA receptor system which is the major inhibitory system in CNS. Contradictory results on the effect of GABAA receptor modulators are reported. Beneficial properties such as anaesthesia, sedation, and anxiolysis are reported as well as adverse, anxiogenic and aggressive effects. It has been suggested that GABAA receptor agonists have bimodal effects. Low concentrations increase an adverse, anxiogenic effect, whereas higher concentrations show beneficial, calming properties.

Aims. To investigate if progesterone treatment induces adverse mood in postmenopausal women and if the severity in mood symptoms is related to progesterone, allopregnanolone or pregnanolone serum concentrations. To evaluate differences in steroid concentrations induced by different doses and routes of administration of progesterone.

Methods. Two randomised, placebo-controlled, double-blind crossover studies of postmenopausal women were performed. Subjects were treated with estradiol continuously. Different doses of progesterone, given vaginally or orally, were added sequentially during the last 14 days of each treatment cycle. Daily symptom ratings were kept using a validated rating scale. Blood samples for progesterone, allopregnanolone and pregnanolone analyses were collected during each treatment cycle. A study regarding the pharmacokinetics after ingestion of low-dose oral progesterone was conducted with postmenopausal women. Blood samples for the analyses of progesterone, allopregnanolone and pregnanolone were collected and pharmacokinetic parameters were calculated.

Results. Certain postmenopausal women on sequential HT with vaginal and oral progesterone experience mood deterioration during the progesterone phase while on a low dose of progesterone but not on higher doses or the placebo. Negative mood symptoms occurred when the serum concentration of allopregnanolone was similar to endogenous luteal phase levels, whereas lower and higher concentrations had no effect on mood. Pharmacokinetic analyses show that low-dose oral progesterone can be used as a prodrug to allopregnanolone when the aim is to achieve physiological concentrations of allopregnanolone.

Conclusions. A bimodal association between allopregnanolone concentration and adverse mood is observed in postmenopausal women treated with progesterone. The addition of low-dose progesterone to estradiol induces adverse mood in postmenopausal women, whereas higher doses and placebo have no mood-deteriorating effect.

sted, utgiver, år, opplag, sider
Umeå: Klinisk vetenskap, 2006. s. 142
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1022
Emneord
Obstetrics and gynaecology, Progesterone, Allopregnanolone, GABA, mood, bimodal, Obstetrik och kvinnosjukdomar
Identifikatorer
urn:nbn:se:umu:diva-785 (URN)91-7264-065-0 (ISBN)
Disputas
2006-06-01, hörsal Betula, 6M, Norrlands Universitetssjukhus, Umeå, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2006-05-03 Laget: 2006-05-03 Sist oppdatert: 2011-04-07bibliografisk kontrollert

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