--- title: Do steroid metabolites differ between women with PMDD and those without? description: Yes. Women with PMDD show different patterns of certain steroid metabolites, particularly sulfated forms, which may relate to how their bodies process hormone url: https://niyora.com/research/papers/the-steroid-metabolome-in-women-with-premenstrual-dysphoric-disorder-during-gnrh-2020/ --- - [Niyora](https://niyora.com/) - [Research](https://niyora.com/research/) - [Library](https://niyora.com/research/library/) - Do steroid metabolites differ between women with PMDD and those without? Randomised trial, 2020 # Do steroid metabolites differ between women with PMDD and those without? Yes. Women with PMDD show different patterns of certain steroid metabolites, particularly sulfated forms, which may relate to how their bodies process hormones. Moderate study design 15 women with confirmed PMDD and 15 women without menstrual cycle mood changes, all medication-free with regular cycles ## What they did Controlled study of 15 women with confirmed PMDD and 15 women without menstrual mood symptoms. All received GnRH agonist treatment to suppress ovaries for 6 months. After 3 months, they were randomly assigned to receive either estradiol or progesterone for 4 weeks, then crossed over to the other hormone after a washout period. Researchers measured 49 steroid metabolites in blood. ## What they found Both groups showed similar baseline metabolite levels and similar increases in some metabolites during hormone treatment. Only sulfated steroid metabolites differed between groups. Women with PMDD had a significantly smaller increase in E2-3-sulfate during estradiol treatment compared to controls. They also showed a decrease in DHEA-sulfate during progesterone treatment while controls showed an increase. ## What it means for you The difference in how women with PMDD process certain steroid metabolites (through sulfation) may explain why their bodies respond differently to hormones. This is a small, controlled study in women selected for hormone sensitivity, so findings need confirmation in larger, more typical PMDD populations. 15 Women with PMDD 15 Control women 49 Steroid metabolites measured ## 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 Rubinow, Gaikwad, Kaddurah-Daouk et al. Journal Carolina Digital Repository (University of North Carolina at Chapel Hill) Year 2020 Study design Randomised trial Participants 21 What was tested GnRH agonist ovarian suppression with estradiol and progesterone addback Open access Yes Read the paper [doi.org/10.17615/fzef-1h40](https://doi.org/10.17615/fzef-1h40) 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<0.2) for multiple comparisons. PMDD and controls had similar basal levels of metabolites during Lupron and P4-derived neurosteroids during Lupron or E2/P4 conditions. Both groups had significant increases in several steroid metabolites compared with the Lupron alone condition after treatment with E2 (that is, estrone-SO4 (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. 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, 2017 Do hormones process differently in women with PMDD? 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