--- title: Do hormones process differently in women with PMDD? | Niyora description: Women with PMDD process certain sulfated steroid hormones differently than others, especially estradiol and DHEA metabolites. The study was very small and tes url: https://niyora.com/research/papers/the-steroid-metabolome-in-women-with-premenstrual-dysphoric-disorder-during-gnrh-2017/ --- - [Niyora](https://niyora.com/) - [Research](https://niyora.com/research/) - [Library](https://niyora.com/research/library/) - Do hormones process differently in women with PMDD? Randomised trial, 2017 # Do hormones process differently in women with PMDD? Women with PMDD process certain sulfated steroid hormones differently than others, especially estradiol and DHEA metabolites. The study was very small and tested only women who were known to be hormone-sensitive, so the findings may not apply to all PMDD. Moderate study design 21 women with PMDD and healthy controls (medication-free, normal menstrual cycles) ## What they did Researchers suppressed ovaries for 6 months in 15 women with PMDD and 15 healthy controls using a hormone injection (GnRH agonist). After 3 months, they added either estradiol or progesterone for 4 weeks each with a 2-week break between. They measured 49 different steroid metabolites in blood samples. ## What they found Only sulfated steroid metabolites showed differences between PMDD and control women. During estradiol treatment, women with PMDD had smaller increases in estradiol-3-sulfate than controls. During progesterone treatment, women with PMDD showed a decrease in DHEA-sulfate while controls showed an increase. No differences were found in progesterone-derived neurosteroids. ## What it means for you Women with PMDD may process hormones differently at a chemical level, which could explain hormone sensitivity. However, this was a very small, highly controlled study in a lab setting, so findings may not reflect what happens with natural menstrual cycles. 21 women in final analysis 49 steroid metabolites measured 6 months ovarian suppression duration ## About the study Original title The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback Authors Nguyen TV, Reuter JM, Gaikwad NW et al. Journal Translational psychiatry Year 2017 Study design Randomised trial Participants 21 What was tested GnRH agonist ovarian suppression for 6 months, with estradiol or progesterone add-back periods Open access Yes Read the paper [doi.org/10.1038/tp.2017.146](https://doi.org/10.1038/tp.2017.146) Original 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 (q 4 (q=0.039 and q=0.002, respectively) and estradiol-3-SO 4 (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. Reproduced under CC-BY. ## Topics [Premenstrual dysphoric disorder (PMDD)](https://niyora.com/research/topics/condition-pmdd/)[Menstrual cycle and mood](https://niyora.com/research/topics/condition-cycle-mood/)[Reproductive hormone sensitivity](https://niyora.com/research/topics/condition-hormone-sensitivity/)[Low mood and depression](https://niyora.com/research/topics/symptom-depression-mood/)[GnRH agonists and ovarian suppression](https://niyora.com/research/topics/treatment-gnrh/)[Neurosteroids (allopregnanolone)](https://niyora.com/research/topics/treatment-neurosteroids/)[Pregnancy and postpartum](https://niyora.com/research/topics/comorbidity-postpartum/) Research tells you what helps on average. Niyora helps on the day it hits. Calm down, see it another way, and decide what to say, with a PMS and PMDD app built by a doctor. ## Related studies Randomised trial, 2020 Do steroid metabolites differ between women with PMDD and those without? 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