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- Bixo, Marie, et al.
(författare)
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Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial
- 2017
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Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 80, s. 46-55
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Tidskriftsartikel (refereegranskat)abstract
- Context: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABA(A) receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.Objective: The objective was to test whether inhibition of allopregnanolone by treatment with the GABA(A) modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.Design: This was an explorative randomized, double-blind, placebo-controlled study.Setting: Swedish multicentre study with 10 centers.Participants: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott's algorithm.Intervention: Subjects were randomized to treatment with UC1010 (10 or 16 mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.Outcome measures: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).Results: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p = 0.041) and borderline significance (p = 0.051) for the sum of Negative mood score. Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n =60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p = 0.006), and for sum of Negative mood score (p=0.003) and impairment (p =0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.Conclusions: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.
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| 2. |
- Turkmen, Sahruh, et al.
(författare)
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Effects of Roux-en-Y gastric bypass surgery on eating behaviour and allopregnanolone levels in obese women with polycystic ovary syndrome
- 2015
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Ingår i: Gynecological Endocrinology. - : Informa Healthcare. - 0951-3590 .- 1473-0766. ; 31:4, s. 301-305
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is associated with abnormal eating habits. We examined whether surgical treatment affected allopregnanolone levels and eating behaviour in nine women with PCOS who qualified for Rou-en-Y gastric bypass surgery. Blood samples were obtained to measure sex-hormone-binding globulin, total testosterone, progesterone, and allopregnanolone, and eating behaviour was evaluated using the Three-Factor Eating Questionnaire before surgery and at 6 and 12 months after surgery. Body mass index and total testosterone levels decreased, and progesterone and sex-hormone-binding globulin levels increased after bariatric surgery compared with pre-surgical values. In patients with anovulatory menstrual cycles, both the serum allopregnanolone level and the allopregnanolone/progesterone ratio were unchanged after surgery. The patients had high uncontrolled and emotional eating scores, and low cognitive restraint scores before surgery, and these scores had improved significantly at 6 and 12 months after surgery. The presurgical allopregnanolone levels were significantly correlated with uncontrolled eating. In conclusion, these results suggest that allopregnanolone appear to be part of the mechanism underlying the abnormal eating behaviour of obese PCOS patients by causing the loss of control over food intake. Roux-en-Y gastric bypass surgery can improve eating behaviour and clinical symptoms, and may facilitate weight loss in obese women with PCOS.
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