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The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback
- Source :
- Translational Psychiatry
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmacometabolomics approach in women with prospectively confirmed PMDD (n=15) and controls without menstrual cycle-related affective symptoms (n=15). All were medication-free with normal menstrual cycle lengths. Notably, women with PMDD were required to show hormone sensitivity in an ovarian suppression protocol. Ovarian suppression was induced for 6 months with gonadotropin-releasing hormone (GnRH)-agonist (Lupron); after 3 months all were randomized to 4 weeks of estradiol (E2) or progesterone (P4). After a 2-week washout, a crossover was performed. Liquid chromatography/tandem mass spectrometry measured 49 steroid metabolites in serum. Values were excluded if >40% were below the limit of detectability (n=21). Analyses were performed with Wilcoxon rank-sum tests using false-discovery rate (q4 (q=0.039 and q=0.002, respectively) and estradiol-3-SO4 (q=0.166 and q=0.001, respectively)) and after treatment with P4 (that is, allopregnanolone (q=0.001 for both PMDD and controls), pregnanediol (q=0.077 and q=0.030, respectively) and cortexone (q=0.118 and q=0.157, respectively). Only sulfated steroid metabolites showed significant diagnosis-related differences. During Lupron plus E2 treatment, women with PMDD had a significantly attenuated increase in E2-3-sulfate (q=0.035) compared with control women, and during Lupron plus P4 treatment a decrease in DHEA-sulfate (q=0.07) compared with an increase in controls. Significant effects of E2 addback compared with Lupron were observed in women with PMDD who had significant decreases in DHEA-sulfate (q=0.065) and pregnenolone sulfate (q=0.076), whereas controls had nonsignificant increases (however, these differences did not meet statistical significance for a between diagnosis effect). Alterations of sulfotransferase activity could contribute to the differential steroid sensitivity in PMDD. Importantly, no differences in the formation of P4-derived neurosteroids were observed in this otherwise highly selected sample of women studied under controlled hormone exposures.
- Subjects :
- 0301 basic medicine
Agonist
Adult
medicine.medical_specialty
Neuroactive steroid
medicine.drug_class
Estrone
medicine.medical_treatment
Pregnanolone
Steroid
03 medical and health sciences
Cellular and Molecular Neuroscience
Basal (phylogenetics)
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Internal medicine
medicine
Humans
Desoxycorticosterone
Biological Psychiatry
Progesterone
Cross-Over Studies
Estradiol
business.industry
Allopregnanolone
Middle Aged
medicine.disease
Psychiatry and Mental health
030104 developmental biology
Endocrinology
chemistry
Pregnanediol
Metabolome
Original Article
Female
Leuprolide
business
Premenstrual Dysphoric Disorder
Premenstrual dysphoric disorder
030217 neurology & neurosurgery
Hormone
Subjects
Details
- Language :
- English
- ISSN :
- 21583188
- Volume :
- 7
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry
- Accession number :
- edsair.doi.dedup.....7e6bb482a0462775bac9c69d5274e59a